Skip to main content
PMC home page
The Journal of Clinical Investigation logoLink to The Journal of Clinical Investigation
. 1975 Aug;56(2):427–437. doi: 10.1172/JCI108109

Antiglobulins and glomerulonephritis. Classification of patients by the reactivity of their sera and renal tissue with aggregated and native human IgG.

R D Rossen, M A Reisberg, J T Sharp, W N Sucki, F X Schloeder, L L Hill, G Eknoyan
PMCID: PMC436603  PMID: 1080158

Abstract

Renal biopsies and sera from 41 consecutive patients were studied to determine if antiglobulins were found more frequently in patients with severely diseased glomeruli. Patients were classified into three groups: A, 12 patients with normal renal function and minimal histological evidence of glomerular disease; B, 18 patients with normal renal function but distinctly abnormal biopsies (16 cases) or proteinuria greater than 16 g/24 h (2 cases); and C, 11 patients with both decreased function and abnormal histology. Positive latex fixation tests for rheumatoid factor were found in none of group A, four (22%) of group B, and five (45%) of group C patients. Sera heated 56 degrees C for 30 min contained precipitins reactive with heat-aggregated IgG in none of seven group A, five of ten (50%) group B, and four of ten (40%) group C patients. The quantity of 135I-labeled patient globulin which bound to immunoadsorbents coated with Cohn fraction II in competition with an equal quantity of 131I-labeled globulin from pooled plasma of normal donors was also measured. Patient globulins bound in significantly greater quantity (greater than or equal 2 SD) than the control in none of the group A, 7 of 18 (39%) group B, and 7 of 11 (64%) group C patients. Renal biopsies from 18 patients were also studied for the ability to fix fluorescein-conjugated heat-aggregated and native human IgG. None of nine tissue specimens from group A or B patients fixed either fluorescein-conjugated protein whereas tissue from eight of nine group C patients showed glomerular localization of one or both reagents. Severity of disease as judged by renal function and glomerular histology correlated with the presence of tissue-fixed and serum antiglobulins. Thus, detection of antiglobulins in glomeruli and sera of patients with glomerulonephritis may indicate a relatively poor prognosis and raises the possibility that antiglobulins may be implicated in some way in the pathophysiology of human glomerulonephritis.

Full text

PDF
437

Images in this article

433Image
on p.433

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Agnello V., Koffler D., Eisenberg J. W., Winchester R. J., Kundel H. G. C1g precipitins in the sera of patients with systemic lupus erythematosus and other hypocomplementemic states: characterization of high and low molecular weight types. J Exp Med. 1971 Sep 1;134(3 Pt 2):228s–241s. [PubMed] [Google Scholar]
  2. Agnello V., Winchester R. J., Kunkel H. G. Precipitin reactions of the C1q component of complement with aggregated gamma-globulin and immune complexes in gel diffusion. Immunology. 1970 Dec;19(6):909–919. [PMC free article] [PubMed] [Google Scholar]
  3. Bacani R. A., Velasquez F., Kanter A., Pirani C. L., Pollak V. E. Rapidly progressive (nonstreptococcal) glomerulonephritis. Ann Intern Med. 1968 Sep;69(3):463–485. doi: 10.7326/0003-4819-69-3-463. [DOI] [PubMed] [Google Scholar]
  4. Carpenter R. R., Reisberg M. A. Carbodiimide-induced bentonite-antigen complexes: readily prepared immunoadsorbents. J Immunol. 1968 Apr;100(4):873–879. [PubMed] [Google Scholar]
  5. Cerottini J. C. An antigen-binding capacity test for human immunoglobulin G (IgG) fragments. J Immunol. 1968 Sep;101(3):433–438. [PubMed] [Google Scholar]
  6. Cochrane C. G., Hawkins D. Studies on circulating immune complexes. 3. Factors governing the ability of circulating complexes to localize in blood vessels. J Exp Med. 1968 Jan 1;127(1):137–154. doi: 10.1084/jem.127.1.137. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Cohen A. S., Canoso J. J. Criteria for the classification of systemic lupus erythematosus--status 1972. Arthritis Rheum. 1972 Sep-Oct;15(5):540–543. doi: 10.1002/art.1780150512. [DOI] [PubMed] [Google Scholar]
  8. EPSTEIN W., JOHNSON A., RAGAN C. Observations on a precipitin reaction between serum of patients with rheumatoid arthritis and a preparation (Cohn fraction II) of human gamma globulin. Proc Soc Exp Biol Med. 1956 Feb;91(2):235–237. doi: 10.3181/00379727-91-22223. [DOI] [PubMed] [Google Scholar]
  9. FAHEY J. L., McCOY P. F., GOULIAN M. Chromatography of serum proteins in normal and pathologic sera: the distribution of protein-bound carbohydrate and cholesterol, siderophilin, thyroxin-binding protein, B12-binding protein, alkaline and acid phosphatases, radio-iodinated albumin and myeloma proteins. J Clin Invest. 1958 Feb;37(2):272–284. doi: 10.1172/JCI103606. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. FARR R. S. A quantitative immunochemical measure of the primary interaction between I BSA and antibody. J Infect Dis. 1958 Nov-Dec;103(3):239–262. doi: 10.1093/infdis/103.3.239. [DOI] [PubMed] [Google Scholar]
  11. Golde D., Epstein W. Mixed cryoglobulins and glomerulonephritis. Ann Intern Med. 1968 Dec;69(6):1221–1227. doi: 10.7326/0003-4819-69-6-1221. [DOI] [PubMed] [Google Scholar]
  12. HELMKAMP R. W., GOODLAND R. L., BALE W. F., SPAR I. L., MUTSCHLER L. E. High specific activity iodination of gamma-globulin with iodine-131 monochloride. Cancer Res. 1960 Nov;20:1495–1500. [PubMed] [Google Scholar]
  13. Hanauer L. B., Christian C. L. Studies of cryoproteins in systemic lupus erythematosus. J Clin Invest. 1967 Mar;46(3):400–408. doi: 10.1172/JCI105541. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. KRAKOWER C. A., GREENSPON S. A. Localization of the nephrotoxic antigen within the isolated renal glomerulus. AMA Arch Pathol. 1951 Jun;51(6):629–639. [PubMed] [Google Scholar]
  15. KUSHNER D. S., ARMSTRONG S. H., Jr, DUBIN A., SZANTO P. B., MARKOWITZ A., MADUROS B. P., LEVINE J. M., RIVER G. L., GYNN TN PENDRAS J. P. Acute glomerulonephritis in the adult. Longitudinal, clinical, functional and morphologic studies of rates of healing and progression to chronicity. Medicine (Baltimore) 1961 May;40:203–240. [PubMed] [Google Scholar]
  16. Koffler D., Agnello V., Carr R. I., Kunkel H. G. Variable patterns of immunoglobulin and complement deposition in the kidneys of patients with systemic lupus erythematosus. Am J Pathol. 1969 Sep;56(3):305–316. [PMC free article] [PubMed] [Google Scholar]
  17. Koffler D., Schur P. H., Kunkel H. G. Immunological studies concerning the nephritis of systemic lupus erythematosus. J Exp Med. 1967 Oct 1;126(4):607–624. doi: 10.1084/jem.126.4.607. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Lewy J. E., Salinas-Madrigal L., Herdson P. B., Pirani C. L., Metcoff J. Clinico-pathologic correlations in acute poststreptococcal glomerulonephritis. A correlation between renal functions, morphologic damage and clinical course of 46 children with acute poststreptococcal glomerulonephritis. Medicine (Baltimore) 1971 Nov;50(6):453–501. [PubMed] [Google Scholar]
  19. MCCLUSKEY R. T., BALDWIN D. S. NATURAL HISTORY OF ACUTE GLOMERULONEPHRITIS. Am J Med. 1963 Aug;35:213–230. doi: 10.1016/0002-9343(63)90213-4. [DOI] [PubMed] [Google Scholar]
  20. MELLORS R. C., NOWOSLAWSKI A., KORNGOLD L., SENGSON B. L. Rheumatoid factor and the pathogenesis of rheumatoid arthritis. J Exp Med. 1961 Feb 1;113:475–484. doi: 10.1084/jem.113.2.475. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Mandalenakis N., Mendoza N., Pirani C. L., Pollak V. E. Lobular glomerulonephritis and membranoproliferative glomerulonephritis: a clinical and pathologic study based on renal biopsies. Medicine (Baltimore) 1971 Jul;50(4):319–355. [PubMed] [Google Scholar]
  22. McCormick J. N., Day J., Morris C. J., Hill A. G. The potentiating effect of rheumatoid arthritis serum in the immediate phase of nephrotoxic nephritis. Clin Exp Immunol. 1969 Jan;4(1):17–28. [PMC free article] [PubMed] [Google Scholar]
  23. McDuffie F. C., Brumfield H. W. Effect of rheumatoid factor on complement-mediated phagocytosis. J Clin Invest. 1972 Dec;51(12):3007–3014. doi: 10.1172/JCI107128. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Meltzer M., Franklin E. C., Elias K., McCluskey R. T., Cooper N. Cryoglobulinemia--a clinical and laboratory study. II. Cryoglobulins with rheumatoid factor activity. Am J Med. 1966 Jun;40(6):837–856. doi: 10.1016/0002-9343(66)90200-2. [DOI] [PubMed] [Google Scholar]
  25. Messner R. P., Laxidal T., Quie P. G., Williams R. C., Jr Serum opsonin, bacteria, and polymorphonuclear leukocyte interactions in subacute bacterial endocarditis. Anti-gamma-globulin factors and their interaction with specific opsonins. J Clin Invest. 1968 May;47(5):1109–1120. doi: 10.1172/JCI105800. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Munthe E. Relationship between IgG complexes and anti-IgG antibodies in rheumatoid arthritis. Acta Rheumatol Scand. 1970;16(3):240–256. [PubMed] [Google Scholar]
  27. Normansell D. E. Anti- -globulins in rheumatoid arthritis sera. II. The reactivity of anti- -globulin rheumatoid factors with altered G-globulin. Immunochemistry. 1971 Jul;8(7):593–602. doi: 10.1016/0019-2791(71)90200-x. [DOI] [PubMed] [Google Scholar]
  28. PLOTZ C. M., SINGER J. M. The latex fixation test. I. Application to the serologic diagnosis of rheumatoid arthritis. Am J Med. 1956 Dec;21(6):888–892. [PubMed] [Google Scholar]
  29. RESTIFO R. A., LUSSIER A. J., RAWSON A. J., ROCKEY J. H., HOLLANDER J. L. STUDIES ON THE PATHOGENESIS OF RHEUMATOID JOINT INFLAMMATION. 3. THE EXPERIMENTAL PRODUCTION OF ARTHRITIS BY THE INTRA-ARTICULAR INJECTION OF PURIFIED 7S GAMMA GLOBULIN. Ann Intern Med. 1965 Feb;62:285–291. doi: 10.7326/0003-4819-62-2-285. [DOI] [PubMed] [Google Scholar]
  30. Reisberg M. A., Rossen R. D., Butler W. T. A method for preparing specific fluorescein-conjugated antibody reagents using bentonite immunoadsorents. J Immunol. 1970 Nov;105(5):1151–1161. [PubMed] [Google Scholar]
  31. Rossen R. D., Butler W. T., Reisberg M. A., Brooks D. K., Leachman R. D., Milam J. D., Mittal K. K., Montgomery J. R., Nora J. J., Rochelle D. G. Immunofluorescent localization of human immunoglobulin in tissues from cardiac allograft recipients. J Immunol. 1971 Jan;106(1):171–180. [PubMed] [Google Scholar]
  32. STEINBERG A. G. POPULATION, IMMUNOGENETIC, AND BIOCHEMICAL STUDIES ON THE GM(B) FACTORS OF HUMAN GAMMA GLOBULIN. Cold Spring Harb Symp Quant Biol. 1964;29:449–454. doi: 10.1101/sqb.1964.029.01.047. [DOI] [PubMed] [Google Scholar]
  33. Unanue E. R., Dixon F. J. Experimental glomerulonephritis: immunological events and pathogenetic mechanisms. Adv Immunol. 1967;6:1–90. doi: 10.1016/s0065-2776(08)60521-0. [DOI] [PubMed] [Google Scholar]
  34. Waller M. Methods of measurement of rheumatoid factor. Ann N Y Acad Sci. 1969 Dec 10;168(1):5–16. doi: 10.1111/j.1749-6632.1969.tb43090.x. [DOI] [PubMed] [Google Scholar]
  35. Wilson C. B., Dixon F. J. Antigen quantitation in experimental immune complex glomerulonephritis. I. Acute serum sickness. J Immunol. 1970 Aug;105(2):279–290. [PubMed] [Google Scholar]
  36. Wilson C. B., Dixon F. J. Quantitation of acute and chronic serum sickness in the rabbit. J Exp Med. 1971 Sep 1;134(3 Pt 2):7s–8s. [PubMed] [Google Scholar]
  37. Winchester R. J., Agnello V., Kunkel H. G. The joint-fluid gammaG-globulin complexes and their relationship to intraarticular complement dimunition. Ann N Y Acad Sci. 1969 Dec 10;168(1):195–203. doi: 10.1111/j.1749-6632.1969.tb43108.x. [DOI] [PubMed] [Google Scholar]
  38. Zvaifler N. J. Further speculation on the pathogenesis of joint inflammation in rheumatoid arthritis. Arthritis Rheum. 1970 Nov-Dec;13(6):895–901. doi: 10.1002/art.1780130621. [DOI] [PubMed] [Google Scholar]

Articles from Journal of Clinical Investigation are provided here courtesy of American Society for Clinical Investigation

RESOURCES