The 100 top-cited studies in systemic lupus erythematosus: A bibliometric analysis

ABSTRACT

Systemic lupus erythematosus (SLE) is an autoimmune inflammatory tissue disease. In view of the explosive growth in research on SLE, bibliometrics was performed to evaluate the 100 top-cited papers in this realm. We performed the search with terms “systemic lupus erythematosus” the Web of Science Core Collection database on May 3, 2023. Relevant literatures were screened. Data were extracted and analyzed by SPSS. The citations of 100 top-cited SLE studies spanned from 472 to 13,557. Most studies (60 out of 100) were conducted in the United States. Total citation times were positively associated with ACY, which was negatively correlated with the length of time since publication. Approximately half of the studies focused on the underlying mechanisms of SLE. New biologic therapies garnered attention and development. Our findings provide valuable insights into the developments in crucial areas of SLE and shed contributions to future studies.

Introduction

Systemic lupus erythematosus (SLE) is an autoimmune connective tissue disease with specific antinuclear antibodies. Although the etiology of the disease is yet to be confirmed, SLE is widely recognized as one of the most classical rheumatic diseases. Numerous studies have put forth the hypothesis that the interaction between congenital and acquired factors may contribute to the excessive production of autoantibodies. The autoantibodies combine with specific autoantigens within the body, forming immune complexes. These immune complexes can then be deposited in various organs such as the skin, joints, small blood vessels, and glomerulus, resulting in multi-system damages.¹ Advancements in immunology and profound investigation into the underlying mechanisms behind SLE have notably prolonged the survival period of individuals diagnosed with SLE. Consequently, this progress has led to the emergence of novel therapeutic approaches in the past decade.^2,3 With increasing incidence rates of SLE in the past decades, a surge of research dedicated to understanding various aspects of the disease such as its pathogenesis, diagnosis, epidemiology, treatment, and prognosis.^4–9 It is valuable to identify the classic article and its profound insights in the realm of SLE.

Bibliometric analysis is a valuable and efficacious instrument for quantitatively evaluating the performance and attributes of publications.¹⁰ Its applications have obtained various fields before, such as tuberculosis, acupuncture, vaccine, allergy, cancer immunotherapy, and so on.^11–15 Citations refer to the frequency at which an article is cited by other articles, and they serve as a valuable metric for assessing and ranking the influence and popularity of research within a specific field. As such, citation count is considered as a quality index for evaluating the impact of an article or journal.¹⁶

Web of Science Core Collection database (WOSCC) is a comprehensive and extensive repository that encompasses major journals across over 170 subject categories. This database offers up-to-date information as well as historical data dating back to 1945. Therefore, a bibliometric analysis was performed to assess the top 100-cited articles related to SLE, utilizing WOSCC, in order to elucidate the distinctive features of these influential articles and ascertain prominent topics and research themes.

Materials and methods

The primary data for this study were sourced from previously published studies, all of which had already obtained ethical approval from their respective ethics committees. Consequently, no additional ethical approval was deemed necessary for the current study.

Search strategy

A comprehensive search was conducted in WOSCC. The search query utilized the topic “systemic lupus erythematosus” and encompassed the entire span from the establishment of the database to May 3, 2023. No language restrictions or other limitations were imposed during the search process. We confirmed researches unrelated to SLE were excluded after reviewing the full text. The 100 top-cited SLE studies were identified in descending order of the number of citations they received.

Data extraction

The data from each study were extracted: title, country, affiliation, first author, publication year, corresponding author, journal, citations, and the publication type. The affiliation and country were determined based on that of the corresponding author. Besides, the objective of each study was categorized into five distinct categories: epidemiology, pathogenesis, diagnosis, therapy, and prognosis. Moreover, a summary of the therapeutic drugs mentioned in the therapy section was also compiled.

Data analysis

The following outcomes, citation times, journal, year, country, affiliation, author, objective of studies, and publication type, were analyzed by IBM SPSS Statistics, version 21 (IBM Corp., Armonk, NY). To assess the normal distribution of the variables, Kolmogorov–Smirnov tests were employed for Average Citations per year (ACY), Citation Time, and Length of time since publication. Correlation for these variables were estimated using Pearson's test for normally distributed data and Spearman's test otherwise.

CiteSpace V (Version 6.1.R2) was utilized to visualize and demonstrate the structure, patterns, and dissemination of scientific knowledge.¹⁷ The nodes in the maps represented institutions, while the connections between nodes represented collaborations. The gauge of the lines indicated the magnitude of the relationship, and the color denoted the year of initial occurrence.

Results

Main characteristics of the selected researches

In the study, the citations of the 100 top-cited papers varied from 472 to 13,557. The most influential papers introduced classification criteria, such as the “1982 revised criteria for the classification of systematic lupus erythematosus.” This was followed by “Updating the American College of Rheumatology revised criteria for the classification of systemic lupus erythematosus,” and the third most impactful article was “Derivation of the SLEDAI-A disease-activity index for lupus patients.” These papers were all published in the Arthritis & Rheumatology journal, which owned 20 of the top 100-cited articles in the field of Rheumatology with impact factor 15.483.^18–20 More details are shown in Table 1.^{1,4,5,7–9, 19–112}

Table 1.

The characteristics of 100 top-cited studies on SLE.

Rank	Article Title	Journal*	Document Type	Times Cited, All Databases	Time since Publication	Average Citations per year
1.	The 1982 Revised Criteria for The Classification of Systemic Lupus Erythematosus	Arthritis Rheum	Article	13557	42	323
2.	Updating The American College of Rheumatology Revised Criteria for The Classification of Systemic Lupus Erythematosus	Arthritis Rheum	Letter	9227	27	342
3.	Derivation of The Sledai – A Disease-Activity Index for Lupus Patients	Arthritis Rheum	Article	4473	32	140
4.	The Fatigue Severity Scale – Application to Patients with Multiple Sclerosis and Systemic Lupus Erythematosus	Arch Neurol	Article	4030	35	115
5.	Derivation and Validation of The Systemic Lupus International Collaborating Clinics Classification Criteria for Systemic Lupus Erythematosus	Arthritis Rheum	Article	3132	12	261
6.	Development of Autoantibodies Before The Clinical Onset of Systemic Lupus Erythematosus	N Engl J Med	Article	2244	21	107
7.	The Development and Initial Validation of The Systemic Lupus International Collaborating Clinics American College of Rheumatology Damage Index for Systemic Lupus Erythematosus	Arthritis Rheum	Article	1968	28	70
8.	Systemic Lupus Erythematosus Disease Activity Index 2000	J Rheumatol	Article	1826	22	83
9.	Murine Models of Systemic Lupus Erythematosus	Adv Immunol	Review	1736	39	45
10.	The Classification of Glomerulonephritis in Systemic Lupus Erythematosus Revisited	J Am Soc Nephrol	Review	1659	20	83
11.	Interferon-Inducible Gene Expression Signature in Peripheral Blood Cells of Patients with Severe Lupus	Proc Natl Acad Sci USA	Article	1604	21	76
12.	Autoantigens Targeted in Systemic Lupus Erythematosus Are Clustered in 2 Populations of Surface-Structures on Apoptotic Keratinocytes	J Exp Med	Article	1589	30	53
13.	Age-Specific Incidence Rates of Myocardial Infarction and Angina in Women with Systemic Lupus Erythematosus: Comparison with The Framingham Study	Am J Epidemiol	Article	1563	27	58
14.	Anti-Cardiolipin Antibodies: Detection by Radioimmunoassay and Association with Thrombosis in Systemic Lupus Erythematosus	Lancet	Article	1457	41	36
15.	The American College of Rheumatology Nomenclature and Case Definitions for Neuropsychiatric Lupus Syndromes	Arthritis Rheum	Review	1455	25	58
16.	Mechanisms of Disease: Systemic Lupus Erythematosus	N Engl J Med	Review	1442	16	90
17.	Interferon and Granulopoiesis Signatures in Systemic Lupus Erythematosus Blood	J Exp Med	Article	1438	21	68
18.	Cd19(+)Cd24(Hi)Cd38(Hi) B Cells Exhibit Regulatory Capacity in Healthy Individuals but Are Functionally Impaired in Systemic Lupus Erythematosus Patients	Immunity	Article	1334	14	95
19.	Systemic Lupus Erythematosus	Orphanet J Rare Dis	Review	1298	18	72
20.	Detection of Immune-Complexes in Unheated Sera By A Modified I-125-C1Q Binding Test – Effect of Heating On Binding of C1Q By Immune-Complexes And Application of Test to Systemic Lupus Erythematosus	J Immunol	Article	1227	48	26
21.	Antibodies To Small Nuclear RNAs Complexed with Proteins Are Produced By Patients with Systemic Lupus Erythematosus	Proc Natl Acad Sci U S A	Article	1206	45	27
22.	Homozygous C1Q Deficiency Causes Glomerulonephritis Associated with Multiple Apoptotic Bodies	Nature Genet	Article	1203	26	46
23.	Antiphospholipid antibodies – anticardiolipin and the Lupus Anticoagulant in Systemic Lupus Erythematosus (SLE) and in Non-SlE Disorders Prevalence and Clinical-Significance	Ann Intern Med	Article	1195	34	35
24.	Epidemiology and Estimated Population Burden of Selected Autoimmune Diseases in The United States	Clin Immunol Immunopathol.	Review	1190	27	44
25.	Prevalence and Correlates of Accelerated Atherosclerosis in Systemic Lupus Erythematosus	N Engl J Med	Article	1113	21	53
26.	Genome Wide Association Scan in Women with Systemic Lupus Erythematosus Identifies Susceptibility Variants in Itgam, Pxk, Kiaa1542 And Other Loci	Nature Genet	Letter	1081	16	68
27.	Bimodal Mortality Pattern of Systemic Lupus-Erythematosus	Am J Med	Article	1073	48	22
28.	Natural History of Systemic Lupus Erythematosus by Prospective Analysis	Medicine (Baltimore)	Review	1047	53	20
29.	A Phase Iii, Randomized, Placebo-Controlled Study of Belimumab, A Monoclonal Antibody That Inhibits B Lymphocyte Stimulator, in Patients with Systemic Lupus Erythematosus	Arthritis Rheum	Article	1043	13	80
30.	Efficacy And Safety of Belimumab in Patients with Active Systemic Lupus Erythematosus: A Randomised, Placebo-Controlled, Phase 3 Trial	Lancet	Article	1017	13	78
31.	Induction of Dendritic Cell Differentiation By IFN-Alpha in Systemic Lupus Erythematosus	Science	Article	999	23	43
32.	Impairment of Neutrophil Extracellular Trap Degradation Is Associated with Lupus Nephritis	Proc Natl Acad Sci U S A	Article	979	14	70
33.	Morbidity And Mortality in Systemic Lupus Erythematosus During A 10-Year Period – A Comparison of Early and Late Manifestations in A Cohort of 1,000 Patients	Medicine (Baltimore)	Article	936	21	45
34.	Reliability And Validity of 6 Systems for The Clinical-Assessment of Disease-Activity in Systemic Lupus Erythematosus	Arthritis Rheum	Article	930	35	27
35.	Netting Neutrophils Are Major Inducers of Type I IFN Production in Pediatric Systemic Lupus Erythematosus	Sci Transl Med	Article	919	13	71
36.	Traditional Framingham Risk Factors Fail to Fully Account for Accelerated Atherosclerosis in Systemic Lupus Erythematosus	Arthritis Rheum	Article	916	23	40
37.	Efficacy And Safety of Rituximab in Moderately-To-Severely Active Systemic Lupus Erythematosus The Randomized, Double-Blind, Phase Ii/Iii Systemic Lupus Erythematosus Evaluation of Rituximab Trial	Arthritis Rheum	Article	885	14	63
38.	Netting Neutrophils Induce Endothelial Damage, Infiltrate Tissues, and Expose Immunostimulatory Molecules in Systemic Lupus Erythematosus	J Immunol	Article	880	13	68
39.	Genome Wide Association Study in A Chinese Han Population Identifies Nine New Susceptibility Loci for Systemic Lupus Erythematosus	Nature Genet	Letter	874	15	58
40.	Neutrophils Activate Plasmacytoid Dendritic Cells By Releasing Self-DNA-Peptide Complexes in Systemic Lupus Erythematosus	Sci Transl Med	Article	860	13	66
41.	Systemic Lupus Erythematosus – Clinical and Immunological Patterns of Disease Expression in A Cohort of 1,000 Patients	Medicine (Baltimore)	Article	815	31	26
42.	Elevated Serum B Lymphocyte Stimulator Levels in Patients with Systemic Immune-Based Rheumatic Diseases	Arthritis Rheum	Article	815	23	35
43.	Mortality in Systemic Lupus Erythematosus	Arthritis Rheum	Article	811	18	45
44.	Characterization of A Rare Il-10-Competent B-Cell Subset in Humans That Parallels Mouse Regulatory B10 Cells	Blood	Article	795	13	61
45.	Toll-Like Receptor 7 And Tlr9 Dictate Autoantibody Specificity and Have Opposing Inflammatory and Regulatory Roles in A Murine Model of Lupus	Immunity	Article	784	18	44
46.	Mycophenolate Mofetil Versus Cyclophosphamide for Induction Treatment of Lupus Nephritis	J Am Soc Nephrol	Article	782	15	52
47.	Nucleic Acids of Mammalian Origin Can Act as Endogenous Ligands for Toll-Like Receptors and May Promote Systemic Lupus Erythematosus	J Exp Med	Article	775	19	41
48.	Heritable Major Histocompatibility Complex Class-Ii-Associated Differences in Production of Tumor Necrosis Factor-Alpha-Relevance to Genetic Predisposition to Systemic Lupus Erythematosus	Proc Natl Acad Sci U S A	Article	765	34	23
49.	Modulatory Effects of 1,25-Dihydroxyvitamin D-3 On Human B Cell Differentiation	J Immunol	Article	759	17	45
50.	Human Lupus Autoantibody-DNA Complexes Activate Dcs Through Cooperation of Cd32 and Tlr9	J Clin Invest	Article	740	19	39
51.	Impaired Phagocytosis of Apoptotic Cell Material By Monocyte-Derived Macrophages from Patients with Systemic Lupus Erythematosus	Arthritis Rheum	Article	737	26	28
52.	Combined Oral Contraceptives in Women with Systemic Lupus Erythematosus	N Engl J Med	Article	731	19	38
53.	Association of Systemic Lupus Erythematosus with C8Orf13-Blk and Itgam-Itgax	N Engl J Med	Article	720	16	45
54.	Premature Coronary Artery Atherosclerosis in Systemic Lupus Erythematosus	N Engl J Med	Review	688	21	33
55.	Immunosuppressive Therapy in Lupus Nephritis – The Euro-Lupus Nephritis Trial, A Randomized Trial of Low-Dose Versus High-Dose Intravenous Cyclophosphamide	Arthritis Rheum	Article	685	22	31
56.	Defective B Cell Tolerance Checkpoints in Systemic Lupus Erythematosus	J Exp Med	Article	683	19	36
57.	Antiphospholipid Antibodies and The Antiphospholipid Syndrome in Systemic Lupus Erythematosus – A Prospective Analysis of 500 Consecutive Patients	Medicine (Baltimore)	Article	679	35	19
58.	Systemic Lupus Erythematosus	Cell	Review	669	28	24
59.	Cutting Edge: A Role For B Lymphocyte Stimulator in Systemic Lupus Erythematosus	J Immunol	Article	668	23	29
60.	Circulating Immune-Complexes in Serum in Systemic Lupus Erythematosus and in Carriers of Hepatitis-B Antigen-Quantitation By Binding to Radiolabeled Clq	J Clin Invest	Article	660	50	13
61.	A Regulatory Polymorphism in Pdcd1 Is Associated with Susceptibility to Systemic Lupus Erythematosus in Humans	Nature Genet	Article	656	22	30
62.	Antibody To Cardiolipin As A Predictor of Fetal Distress or Death in Pregnant Patients with Systemic Lupus Erythematosus	N Engl J Med	Article	652	39	17
63.	A Subset of Lupus Anti-DNA Antibodies Cross-Reacts with The Nr2 Glutamate Receptor in Systemic Lupus Erythematosus	Nat Med	Article	652	23	28
64.	Heart in Systemic Lupus-Erythematosus And Changes Induced in It By Corticosteroid-Therapy – Study of 36 Necropsy Patients	Am J Med	Article	648	49	13
65.	A Large-Scale Replication Study Identifies Tnip1, Prdm1, Jazf1, Uhrf1Bp1 and Il10 As Risk Loci for Systemic Lupus Erythematosus	Nature Genet	Article	647	15	43
66.	Range of Antinuclear Antibodies in ’‘Healthy’’ Individuals	Arthritis Rheum	Article	642	27	24
67.	Type I Interferon in Systemic Lupus Erythematosus and Other Autoimmune Diseases	Immunity	Review	632	18	35
68.	The Antiphospholipid Syndrome − 10 Years On	Lancet	Review	631	31	20
69.	Thrombosis in Systemic Lupus Erythematosus-Striking Association with The Presence of Circulating Lupus Anticoagulant	BMJ	Article	625	41	15
70.	B Cell Depletion as A Novel Treatment for Systemic Lupus Erythematosus – A Phase I/Ii Dose-Escalation Trial of Rituximab	Arthritis Rheum	Article	623	20	31
71.	Defective Reticuloendothelial System Fc-Receptor Function in Systemic Lupus Erythematosus	N Engl J Med	Article	620	45	14
72.	A Revised Estimate of Twin Concordance in Systemic Lupus Erythematosus	Arthritis Rheum	Article	617	32	19
73.	Features of Systemic Lupus Erythematosus in Dnase1-Deficient Mice	Nature Genet	Letter	601	24	25
74.	Microrna-146A Contributes to Abnormal Activation of The Type I Interferon Pathway in Human Lupus By Targeting The Key Signaling Proteins	Arthritis Rheum	Article	601	15	40
75.	Accelerated In-Vitro Apoptosis of Lymphocytes from Patients with Systemic Lupus Erythematosus	J Immunol	Article	599	30	20
76.	The Epidemiology of Autoimmune Diseases	Autoimmun Rev	Review	591	21	28
77.	2 Small Rnas Encoded By Epstein Barr Virus and Complexed with Protein Are Precipitated By Antibodies From Patients with Systemic Lupus Erythematosus	Proc Natl Acad Sci	Article	586	43	14
78.	The Reliability of The Systemic Lupus International Collaborating Clinics American College of Rheumatology Damage Index in Patients with Systemic Lupus Erythematosus	Arthritis Rheum	Article	586	27	22
79.	Continuous Administration of Anti-Interleukin-10 Antibodies Delays Onset of Autoimmunity in Nzb/W F1-Mice	J Exp Med	Note	584	30	19
80.	Clinical Efficacy and Side Effects of Antimalarials in Systemic Lupus Erythematosus: A Systematic Review	Ann Rheum Dis	Review	581	14	42
81.	Neuropsychiatric Manifestations of Systemic Lupus Erythematosus Diagnosis, Clinical Spectrum, and Relationship to Other Features of Disease	Medicine	Article	578	48	12
82.	Autoantibodies in The Diagnosis of Systemic Rheumatic Diseases	Semin Arthritis Rheum	Review	577	29	20
83.	Pathogenesis of Systemic Lupus Erythematosus	J Clin Pathol	Review	574	21	27
84.	The Risk of Lymphoma Development in Autoimmune Diseases – A Meta-Analysis	Arch Intern Med	Review	559	19	29
85.	Disturbed Peripheral B Lymphocyte Homeostasis in Systemic Lupus Erythematosus	J Immunol	Article	553	24	23
86.	Autoimmune Diseases Induced By Tnf-Targeted Therapies – Analysis of 233 Cases	Medicine (Baltimore)	Article	552	17	32
87.	A Hierarchical Role for Classical Pathway Complement Proteins in The Clearance of Apoptotic Cells in Vivo	J Exp Med	Article	544	24	23
88.	Systemic Lupus Erythematosus	Lancet	Review	544	17	32
89.	Risk Factors for Coronary-Artery Disease in Patients with Systemic Lupus Erythematosus	Am J Med	Article	542	32	17
90.	Expanded Double Negative T Cells in Patients with Systemic Lupus Erythematosus Produce Il-17 And Infiltrate The Kidneys	J Immunol	Article	540	16	34
91.	Genetic Association of The R620W Polymorphism of Protein Tyrosine Phosphatase Ptpn22 with Human SLE	Am J Hum Genet	Article	537	20	27
92.	Epidemiology of Systemic Lupus Erythematosus: A Comparison of Worldwide Disease Burden	Lupus	Review	525	18	29
93.	Epidemiological Studies in Incidence, Prevalence, Mortality, and Comorbidity of The Rheumatic Diseases	Arthritis Res Ther	Article	519	15	35
94.	A Common Haplotype of Interferon Regulatory Factor 5 (Irf5) Regulates Splicing and Expression and Is Associated with Increased Risk of Systemic Lupus Erythematosus	Nature Genet	Article	517	18	29
95.	Role of Interleukin-10 in The B Lymphocyte Hyperactivity and Autoantibody Production of Human Systemic Lupus Erythematosus	J Exp Med	Review	514	29	18
96.	Mechanisms of Disease Systemic Lupus Erythematosus	N Engl J Med	Review	512	13	39
97.	Expansion of Circulating T Cells Resembling Follicular Helper T Cells Is A Fixed Phenotype That Identifies A Subset of Severe Systemic Lupus Erythematosus	Arthritis Rheum	Article	512	14	37
98.	The Bilag Index – A Reliable and Valid Instrument for Measuring Clinical Disease Activity in Systemic Lupus Erythematosus	Q J Med	Review	496	31	16
99.	Defective Production of Interleukin-1 and Interleukin-2 in Patients with Systemic Lupus Erythematosus	J Immunol	Article	483	41	12
100.	Understanding The Epidemiology and Progression of Systemic Lupus Erythematosus	Semin Arthritis Rheum	Review	472	14	34

* The journals’ acronym is derived from Web of Science.

Distribution by institution

The institutions involved in the 100 most highly cited studies are presented in Figure 1. Considering the institutions associated with all authors in the included studies, the following institutions were ranked according to their prominence: Johns Hopkins University, University College London, Harvard University, Oklahoma Medical Research Foundation, Baylor Institute for Immunology Research, Cornell University, and University of California, San Francisco.

Figure 1.

Institutions of the corresponding author in the 100 top-cited studies.

In this network visualization, nodes represent all institutions included in the 100 top-cited studies, while the links between nodes indicate the relationships between these institutions. The size of each node corresponds to the number of papers published by the respective institution. Additionally, the thickness of the links reflects the strength of the relationship between the institutions. To further enhance clarity, the years of first co-occurrence have been color-coded in a gradient from gray to purple, blue, green, yellow, orange, and finally red. This coding scheme indicates a progressive increase over the years, spanning from 1971 to 2012.

In addition, 18 institutions conducted multiple studies as the institution of corresponding author on SLE. Johns Hopkins University conducted the most articles with six studies, followed by Harvard University (n = 4) and Baylor Institute for Immunology Research (n = 4).

Distribution by publication year

Figure 2 displays the included studies that spanned from 1971 to 2012. The year 2003 saw the highest number of studies (n = 8), closely followed by 2011 (n = 7). In terms of citations, 1982 recorded the highest count with 13,557 citations, followed by 1997 with 13,208 citations. Furthermore, the years 1982 and 2012 stood out with maximum citations per article: 13557 in 1982 and 3,132 citations per article in 2012. Notably, the two most cited papers, published 42 and 27 years ago, respectively, focused on the diagnosis of SLE and laid a robust foundation for future SLE research.

Figure 2.

Years of the 100 top-cited studies on SLE.

Distribution by journal

Among them, the 100 classic studies were distributed across 34 journals as outlined in Table 2. Notably, the journal “Arthritis & Rheumatology” had maximum studies (n = 20) and amassed a total citation count of 44,215. It was closely followed by “The New England Journal of Medicine” with nine studies and a total citation count of 8,722. Regarding the average citations per article, “Archives of Neurology” ranked the highest with an average of 4,030 citations per article, followed by “The Journal of Arthritis & Rheumatology” with 2,211 citations per article.

Table 2.

The journals of the 100 top-cited studies in SLE.

Journal	Total Citation Times	Number	Average Citation Times
Arthritis & Rheumatology	44215	20	2211
The New England Journal of Medicine	8722	9	969
Journal of Experimental Medicine	6127	7	875
Journal of Immunology	5709	8	714
Nature Genetics	5579	7	797
Proceedings of the National Academy of Sciences of The United States of America	5140	5	1028
Medicine	4607	6	768
Archives of Neurology	4030	1	4030
Lancet	3649	4	912
Immunity	2750	3	917
Journal of the American Society of Nephrology	2441	2	1221
American Journal of Medicine	2263	3	754
Journal of Rheumatology	1826	1	1826
Science Translational Medicine	1779	2	890
Advances In Immunology	1736	1	1736
American Journal of Epidemiology	1563	1	1563
Journal of Clinical Investigation	1400	2	700
Orphanet Journal of Rare Diseases	1298	1	1298
Annals of Internal Medicine	1195	1	1195
Clinical Immunology and Immunopathology	1190	1	1190
Seminars In Arthritis and Rheumatism	1049	2	525
Science	999	1	999
Blood	795	1	795
Cell	669	1	669
Nature Medicine	652	1	652
British Medical Journal	625	1	625
Autoimmunity Reviews	591	1	591
Annals of the Rheumatic Diseases	581	1	581
Journal of Clinical Pathology	574	1	574
Archives of Internal Medicine	559	1	559
American Journal of Human Genetics	537	1	537
Lupus	525	1	525
Arthritis Research and Therapy	519	1	519
Quarterly Journal of Medicine	496	1	496

Distribution by publication type

Based on the types of publications, out of the total 100 studies, 73 were articles (Table S1), 22 were reviews, four were letters, and one was a note.

Distribution by author

Among the authors involved, eleven served as corresponding authors for multiple studies, while six authors were first authors for multiple studies (Table 3). Michelle Petri conducted the highest number of studies as the first author (n = 3), focusing on the diagnosis criteria, risk factors, and prognosis of SLE. Meanwhile, Graham R.V. Hughes published the most studies as corresponding authors (n = 5), covering the thrombosis aspect and epidemiology of SLE.

Table 3.

Authors with at least two studies as first author or corresponding author in the 100 top-cited studies on SLE.

Authorship	Name	Number of studies
Corresponding author	Graham R.V. Hughes	5
	Timothy W. Behrens	3
	Virginia Pascual	3
	Marc C Hochberg	2
	Asad Zoma	2
	Joan Argetsinger Steitz	2
	Mark J Walport	2
	P. A. Miescher	2
	Marta E Alarcón-Riquelme	2
	Munther A Khamashta	2
	George C Tsokos	2
First author	Michelle Petri	3
	MD Eng M. Tan	2
	Gladman, DD	2
	Matthew H Liang	2
	Michael Rush Lerner	2
	Ricard Cervera	2

Distribution by country

We employed the countries of the corresponding authors to analyze the country distributions. In brief, these studies were contributed by authors from a total of 14 countries (the United States, England, Canada, Spain, China, Switzerland, Germany, Sweden, Australia, Belgium, France, Mexico, the Netherlands, and Greece) (Figure 3). The average citation count for each country was delineated as the aggregate citation count within the country where the affiliation of the corresponding author was situated, divided by the total number of articles.

Figure 3.

Country distribution of the 100 top-cited studies on SLE.

The country with maximum studies was the USA (n = 60), then England (n = 11), Canada (n = 6), Spain (n = 4), and Germany (n = 4). In terms of total citations, the USA also topped the list with 79,298 citations, while England followed with 10,356 citations, Canada with 9685 citations. The country that had maximum citations on average was the Netherlands with 1,659 citations, followed by Canada with 1,614 citation times, and the USA with 1321 times.

In addition, considering the impact of the resident population, we defined the citation rate per million residents as the total number of citations divided by the resident population of the country. The top three countries in this regard were Switzerland (305 citations per million residents), Canada (242 citations per million residents), and the USA (234 citations per million residents), followed by England (185 citations per million residents) and Sweden (107 citations per million residents).

Distribution by topic

Among the 100 top-cited studies on SLE, approximately half of them probed into the potential mechanisms of SLE. These studies have laid the groundwork for identifying potential therapeutic targets and diagnostic criteria. The three top-cited papers focused on the classification criteria and evaluation of disease activity. Specifically, the American Rheumatism Association 1982 criteria, the American College of Rheumatology 1997 criteria, and the Systemic Lupus International Collaborating Clinics classification 2012 criteria were considered to be classic references.^18,19,89 Furthermore, classification criteria in specific areas have been extensively cited by experts. For instance, one paper detailed the classification of glomerulonephritis in SLE, while another provided a definition for neuropsychiatric lupus syndrome.^76,108 Additionally, there were seven studies focused on the epidemiology of SLE, while nine studies investigated various therapeutic approaches for the disease (Table 4).

Table 4.

Objective distribution in the 100 top-cited studies on SLE.

Category	Subgroup	Number of studies
Pathogenesis	T cell	3
	B cell	14
	Dendritic cell	2
	Macrophage	2
	Neutrophil	3
	Cytokine	8
	Gene	7
	Other	7
Prognosis		17
Diagnosis		21
Epidemiology		7
Therapy	Biologic therapy	5
	Immunosuppressive drugs	2
	Antimalarial agents	1
	Corticosteroids	1

There were 46 studies examining the pathogenesis of the disease. Out of these, 14 papers specifically focused on B cells, 3 on T cells, 2 on dendritic cells, 2 on macrophages, 3 on neutrophils, 8 on cytokines, 7 on genes, and the remaining 7 were categorized under “other” subtypes.

The drugs mentioned in the nine studies encompassed Belimumab, Rituximab, TNF-targeted therapy, cyclophosphamide, azathioprine, mycophenolate mofetil, antimalarials, and corticosteroids. Out of these nine studies, five focused on biologic therapy, two explored immunosuppressive drugs, one studied antimalarial agent, and the remaining one examined corticosteroid. Further details can be seen in Table 4.

Correlation analysis between total citation times, ACY, and publication time

The distribution of ACY, total citations, and the length of time since publication deviated from the normal distribution. Therefore, Spearman tests were employed to analyze their correlation. The results suggested that ACY was negatively correlated with the length of time since publication (r = 0.706, p < .001) (Figure 4), while total citation times were positively associated with ACY (r = −0.577, p < .001) (Figure 5). However, no correlation was found between the total citation times and the time elapsed since publication.

Figure 4.

Correlation analysis between ACY and publication time.

ACY: Average citations per year.

Figure 5.

Correlation analysis between total citation times and ACY.

ACY: Average citations per year.

The top 10 most cited articles in SLE in the past decade

The 100 top-cited studies about SLE spanned from 1971 to 2012 may not adequately represent the recent contributions of rheumatologists in the era of SLE in the past 10 years. Hence, we conducted a comprehensive review of the literature on SLE published from 2013 to 2023. A comprehensive search with the keyword “systemic lupus erythematosus” was conducted in WOSCC on May 20, 2023. Through a comprehensive review of full-text articles, it was ensured that studies unrelated to SLE were excluded. The ten top-cited SLE studies were identified in descending order of the number of citations they received. Table 5 displays the detailed characteristics of the ten top-quoted studies during this period.^113–122 The citation counts for these top-cited studies ranged from 180 to 403. The most influential study in the era of SLE remained an update on the diagnostic criteria, closely followed by the management recommendations for SLE. Among the ten top-cited articles published between 2014 and 2020, three of them were published in the prestigious journal Annals of the Rheumatic Diseases.

Table 5.

The ten top-cited studies in systemic lupus erythematosus from 2013 to 2023.

Rank	Article Title	Journal*	Document Type	Times Cited, All Databases	Publication Year
1	2019 European League Against Rheumatism/American College of Rheumatology Classification Criteria for Systemic Lupus Erythematos	Arthritis Rheum	Article	403	2019
2	2019 update of the EULAR recommendations for the management of systemic lupus erythematosus	Ann Rheum Dis	Article	361	2019
3	New insights into the immunopathogenesis of systemic lupus erythematosus	Nat Rev Rheumatol	Review	366	2016
4	Systemic lupus erythematosus	Nat Rev Dis Primers	Review	280	2016
5	Systemic lupus erythematosus	Lancet	Review	278	2014
6	Anifrolumab, an Anti-Interferon-alpha Receptor Monoclonal Antibody, in Moderate-to-Severe Systemic Lupus Erythematosus	Arthritis Rheum	Article	269	2017
7	Trial of Anifrolumab in Active Systemic Lupus Erythematosus	N Engl J Med	Article	243	2020
8	Treat-to-target in systemic lupus erythematosus: recommendations from an international task force	Ann Rheum Dis	Review	215	2014
9	Genetic association analyses implicate aberrant regulation of innate and adaptive immunity genes in the pathogenesis of systemic lupus erythematosus	Nat Genet	Article	323	2015
10	EULAR recommendations for women’s health and the management of family planning, assisted reproduction, pregnancy and menopause in patients with systemic lupus erythematosus and/or antiphospholipid syndrome	Ann Rheum Dis	Article	180	2017

 * The journals’ acronym is derived from Web of Science.

Discussion

In recent decades, research on SLE has experienced significant growth, as evident from bibliometric analysis that sheds light on the historical development trends in this realm of SLE. The citation counts of the included studies on SLE varied from 472 to 13,557. Notably, the two most highly cited studies were both focused on the classification criteria of SLE and were published in the journal “Arthritis & Rheumatology.” Moreover, the citation counts in the SLE field were comparable to those observed in the diabetes field, where the top 100 cited studies ranged from 1,121 to 10,292 citations.¹²³ Furthermore, these numbers surpassed those observed in urology studies (ranging from 418 to 1,435 citations) and Hepatitis E virus studies (ranging from 148 to 791 citations).^13,124 Variation in citations across different fields may indicate differences in the number of researchers actively involved in specific areas. The considerable citation figures also highlight the popularity of research on SLE diseases, illustrating the abundance of relevant studies conducted in this era of SLE.

The included 100 studies originated from 14 countries. Sixty of the 100 studies were performed in the United States, with a significant proportion of institutions also located within the country. Furthermore, the United States, the United Kingdom, and Canada emerged as the primary countries where the leading SLE studies were conducted, mirroring the trends observed in the fields of lung cancer and hypertension.^125,126

Approximately half of these studies focused on investigating the potential mechanisms underlying SLE. To delve deeper into the pathogenesis of SLE, researchers classified the underlying mechanisms into eight categories: B cell, T cell, dendritic cell, macrophage, neutrophil, cytokine, gene, and other. The majority of studies in this field have primarily focused on the role of B cells in the pathogenesis of SLE. Abnormalities in early B cell tolerance within the bone marrow were proved to be pivotal factors in the onset of SLE. In terms of adaptive immune activation, Toll-like receptor 7 (TLR-7) was important in the immune dysregulation observed in SLE. Additionally, the B lymphocyte stimulator (BLyS) has been confirmed to be a valuable marker for early autoimmune diathesis and activation of autoreactive B cells in human SLE.^5,110 Over the past few decades, numerous experts have further explored the abundance and functionality of different B cell subtypes. For instance, CD19(+) CD24(hi) CD38(hi) B cells were demonstrated to exhibit a refractory response to CD40 stimulation and produce lower levels of IL-10 when compared to healthy controls.³⁰

Regarding T cells, double negative cells in SLE patients produced a large amount of IL-17 and IFN- γ, stimulating anti CD3 antibodies in the presence of helper cells in vitro.⁴⁰ Experts have suggested that the abnormal apoptosis of lymphocytes in SLE may serve as a source of extracellular nuclear antigens, contributing to immune responses and the formation of immune complexes.⁴⁶

Among the 100 most highly cited studies, three specifically investigated the involvement of neutrophils in SLE pathogenesis. Neutrophil extracellular traps (NETs) were composed of DNA and neutrophil proteins that assist plasmacytoid dendritic cells (pDCs) to uptake and identify mammalian DNA.⁷³ Through Toll-like receptor 9 (TLR9), NETs effectively generated and triggered innate pDC activation. Importantly, the production of autoantibodies against their own DNA present in NETs was found in individuals with SLE, indicating that these complexes can also serve as autoantigens in initiating B cell activation.^53,73 Impaired phagocytosis of apoptotic cells by macrophages has been observed in SLE patients. Continuously circulating apoptotic remnants acted as an immunogen, driving the activation of autoreactive lymphocytes and the formation of immune complexes, and thus triggering the incidence of SLE.⁶²

The medications discussed in the nine studies encompassed Belimumab, Rituximab, TNF-targeted therapy, cyclophosphamide, azathioprine, mycophenolate mofetil, antimalarials, and corticosteroids. In the twentieth century, primary treatments for SLE consisted of corticosteroids, antimalarial agents, and immunosuppressive drugs. While corticosteroids proved effective in SLE, they were also associated with higher risks of short-term and long-term complications.³⁴ In a study by Condon, M. B. et al., it was found that low-dose corticosteroids had equivalent efficacy but lower rates of complications compared to traditional-dose therapy.¹²⁷ Antimalarial drugs, namely chloroquine and hydroxychloroquine, are recommended for continuous use throughout the course of SLE, with the exception of medical contraindications.⁹⁶ In terms of immunosuppressants, mycophenolate mofetil has demonstrated comparable efficacy to cyclophosphamide in the induction therapy of lupus nephritis.²³ Additionally, the remission rates achieved through the induction therapy for lupus nephritis were comparable between low-dose cyclophosphamide followed by azathioprine and high-dose cyclophosphamide.⁸ As a result, monotherapy with mycophenolate mofetil or cyclophosphamide has been established as the standard treatment approach. However, there have recently been FDA-approved options for dual-therapy and targeted therapies. Additionally, other immunosuppressants such as tacrolimus, azathioprine, calcineurin inhibitors, and methotrexate are frequently utilized in various clinical scenarios.

In light of the side effects associated with the aforementioned therapies, a considerable number of research is dedicated to study biologics, including antibodies that target B cells, T cells, cytokines, and signaling molecules. In patients with SLE, abnormal activation of B cells has been observed. Therefore, inhibiting B cell-associated receptors and preventing the activation of cytokines and signaling molecules are key areas in the development of SLE biologics. In the early twenty-first century, several randomized, double-blind trials were conducted for Belimumab and Rituximab. Rituximab, a monoclonal antibody targeting CD20-positive B cells, has been a subject of extensive research in recent decades. However, Rituximab did not achieve primary endpoints in phase I/II/III trials.^80,83 Nevertheless, the administration of Rituximab on days 1 and 15 in combination with methylprednisolone, along with the maintenance treatment of mycophenolate mofetil, has been demonstrated to yield a remarkable 90% rate of complete biochemical remission.¹²⁷ Hence, Rituximab has been acknowledged as a valuable alternative for individuals who are unable to tolerate the side effects of, or are ineffective with conventional therapies.^80,83,128 On the other hand, Belimumab, a monoclonal antibody selectively inhibiting BLys, effectively impedes the combination of BLys to its receptor on B cells. Therefore, this mechanism leads to a decrease in B cell survival, differentiation, and activation. Furthermore, in a phase III study, it was demonstrated that Rituximab outperformed placebo in alleviating SLE symptoms.^51,85 Belimumab and Rituximab are both currently in Phase IV clinical trial stage. Recent studies have shown that their combined use could significantly reduce serum anti-dsDNA titers and improve clinical symptoms of SLE patients.¹²⁹ In addition, Obexelimab is a bispecific antibody targeting CD19 and the FcγRIIb receptor on B cell surfaces. Approximately 50% of the patients treated with Obexelimab experienced a reduction in B cell numbers.¹³⁰ Notably, both Rituximab and Belimumab were included in the list of the 100 most-cited articles, highlighting their significance as major biologic therapies in clinical practice.

T cell co-stimulation blockers also play a significant role in the field of SLE. The immune activation of B cells relies on co-stimulatory signals and interactions with T cells. The cytotoxic T lymphocyte-associated protein 4 (CTLA-4) competitively binds to CD80/CD86, inhibiting B cell growth and activation. Abatacept, a CTLA-4 analog, has shown promising results in a Phase III clinical trial for patients with SLE.¹³¹ In the field of pDCs, two molecules directly target pDCs, Litifilimab and Daxdilimab, also showing promising potential in early clinical trials.

Over the past decade, significant advancements have been made in biologic drugs associated with cytokines in the realm of SLE. These include Anifrolumab (a monoclonal antibody blocking IFNAR), Baricitinib (an inhibitor of JAK1 and JAK 2), Ustekinumab (a monoclonal antibody that specifically targets IL-12 and IL-23), and so on.^132–135 Notably, Anifrolumab, an anti-IFNα mAb, was granted FDA approval for the remedy of SLE in 2021, marking a significant milestone in the field of SLE therapeutics.

This is the first study to assess the top 100-cited articles related to SLE, in order to elucidate the distinctive features of these influential articles and ascertain prominent topics and research themes. Previous bibliometric investigations on SLE encompassed all articles published within specific timeframes.¹³⁶ In contrast, our study pioneered a focus on scrutinizing seminal articles within the SLE domain boasting the highest citation counts. By narrowing our scope to the top 100 most cited papers, our aim was to pinpoint a more condensed collection of influential and widely acknowledged contributions within the realm of SLE. Moreover, considering the impact of publication dates on citation frequencies, we incorporated the ACY concept and conducted correlation analyses between total citation counts, ACY, and publication times to identify the effect of the time since publication on the citation times.

This study also has several limitations. First, the accuracy of article selection cannot be guaranteed, which is an inherent weakness of all bibliometric analyses.¹³⁷ Second, self-citation can also lead to citation bias, which may have a potential bias on our result.¹⁶ Third, although we have confirmed that there was no correlation between the total number of citations and the length of time after publication, this is a cross-sectional study and citation times may be affected by publication year. Finally, some high-quality studies, which define a specific disease, manifestation, disease activity, or damage accrual in niche areas of SLE, have not been widely cited. This may result in missing potential high-quality articles.

Conclusion

This study performed a bibliometric analysis of highly cited studies in the field of SLE. We found that the citation times were rising and most of the highly cited articles were conducted in a limited number of countries. Furthermore, approximately half of the studies investigated the potential mechanisms underlying SLE. The drugs frequently mentioned in the 100 top-cited studies on SLE encompassed corticosteroids, antimalarial agents, immunosuppressive drugs, and biologic therapies. Notably, the newly emerged biologic therapies garnered the highest number of citations, highlighting their increasing significance in the field. This comprehensive review offers a valuable compilation of influential references relevant to SLE, potentially serving as a source of inspiration for future research endeavors.

Biographies

Liuliu Quan is a PhD candidate at the Department of Rheumatology and Immunology at Peking Union Medical College Hospital. She has published numerous SCI articles in leading international rheumatology and immunology journals.

Jiawen Dai is a PhD candidate at the institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College. She specializes in blood and immunological diseases for several years and has published numerous SCI articles in hematology and immunology journals.

Yuan Luo graduated from the School of Public Health at Sichuan University, majoring in preventive medicine. She is currently pursuing a master’s degree at Sichuan University, majoring in health policy and management, and has participated in many scientific research projects on campus.

Lin Wang graduated from the School of Clinical Medicine at Southwest Medical University, majoring in clinical medicine. She currently specializes in dermatology and has participated in many scientific research projects in related fields.

Yue Liu is an undergraduate student majoring in preventive medicine at the West China School of Public Health, Sichuan University, who has participated in some scientific research projects and has a certain medical foundation, and has published articles in core journals.

Jiaqi Meng is an undergraduate student at the West China School of Public Health, Sichuan University. During her studies, she has been active in the Student Union, participated in scientific research projects led by faculty, and conducted experiments.

Fan Yang is a student at the West China School of Medicine, Sichuan University, majoring in public health. With a strong interest in non-communicable chronic diseases, she is particularly focused on health promotion for patients with tumors. She has participated in various research projects aimed at understanding and mitigating public health issues, especially in the areas of cancer prevention and treatment.

Xin You is a Chief Physician at the Department of Rheumatology and Immunology at Peking Union Medical College Hospital. She has worked in the Rheumatology and Immunology Departments at Yale University, the University of California, San Diego, and New York University School of Medicine. She holds a Doctorate in Medicine, is a full professor, and supervises doctoral students. With over 20 years of clinical experience in rheumatic and immunological diseases, she specializes in diagnosing and treating complex cases. As the principal investigator, she has led several projects funded by the National Natural Science Foundation of China and has published numerous SCI articles in leading international rheumatology and immunology journals.

Funding Statement

The author(s) reported that there is no funding associated with the work featured in this article.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Authors’ contributions

All authors contributed to the study conception and design. YX, QL, and DJ performed the data collection. LY and WL were responsible for the data interpretation. QL, DJ, and LY performed data analysis. LY, MJ, and YF undertook the figures. All authors wrote the first draft of the manuscript. YX was the study guarantor, reviewing the paper. LQ, QL, and DJ made critical revision of the manuscript for important intellectual content. All authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

Data availability statement

The data underlying this article will be shared on reasonable request to the corresponding author.

Supplementary material

Supplemental data for this article can be accessed on the publisher’s website at https://doi.org/10.1080/21645515.2024.2387461