Table 2. Genetic and immunologic mechanisms in the correlation of type 1 diabetes and celiac disease.

CD: celiac disease; HLA: human leukocyte antigen; KIR: killer immunoglobulin-like receptor; T1DM: type 1 diabetes mellitus

Study	Author	Year	Type of study	Purpose of the study	Results	Conclusion
1	Siddiqui et al. [3]	2021	Cross-sectional	Evaluate the use of HLA typing for diagnosis of CD	31.4% of patients with T1DM tested positive for CD allele DQ2, 25% for allele DQ8, and 34% for both	The HLA testing can aid in the diagnosis of CD in patients without previously known disease
2	Farina et al. [14]	2019	Cross-sectional	Measure the expression of high-risk genes HLA-DQ2.5 and DQ8 and their importance in the activation of CD4 lymphocytes	Elevated expression of high-risk alleles encoding for genes: DQA1*05 and DQB1*02 coding for HLA-DQ2.5. DQA1*03 and DQB1*03 coding for HLA-DQ8	Elevated expression of high-risk alleles confers an increased risk for developing autoimmunity
3	Bhadada et al. [5]	2017	Cross-sectional	Extrapolate the biochemical, hormonal, and clinical presentations in CD vs CD+T1DM patients	CD was diagnosed in a mean of 48.8±43.4 months after T1DM diagnosis	CD is diagnosed earlier in patients with T1DM compared with patients without T1DM
4	Hagopian et al. [17]	2017	Cohort	Find out if T1DM trigger CD and if their coexistence occurs by inheritance of the same genes	The study demonstrates a 32% greater prevalence of tissue transglutaminase antibodies in patients with islet autoantibodies	T1DM and CD coexistence occurs more than expected
5	Mitchell et al. [15]	2016	Cross-sectional	Demonstrate if HLA-DQ testing for CD screening in T1DM patients is cost-effective	CD was diagnosed in 6.9% of patients studied. 94% of patients carried HLA-DQ2 and/or HLA-DQ8 which are high-risk alleles	It is not cost-effective to test all patients with T1DM for HLA-DQ genotyping due to the high rate of positive results and co-occurrence of these diseases
6	Gutierrez-Achury et al. [1]	2015	Case-control	Compare the genetic variances among patients with CD and T1DM, and patients with just one of the two diseases using genome-wide association studies (GWAS)	Eight risk alleles among 60 were present in patients with both diseases; HLA-DQ2.5 was significantly associated with double autoimmunity	Genetic risk for double autoimmunity is increased with HLA class II
7	Akar et al. [17]	2015	Cohort	Demonstrate the role of KIR genes, KIR/HLA class I ligand combinations, and HLA class I in the development of CD and T1DM cooccurrence	KIR genes 2DS5 and 3DS1 were more frequent in patients with both diseases. The presence of HLA-C1 ligand was more frequent in the group with coexistence of CD and T1DM. Activating combinations of KIR genes and HLA-ligands were more frequent in the group with both diseases	The presence of KIR genes 2DS5, 3DS1, and HLA-C1 ligand are a risk factor for CD and coexistence of CD and T1DM, as well, as the activating combinations of genes and ligands