Skip to main content
NCBI home page
The American Journal of Pathology logoLink to The American Journal of Pathology
. 1978 May;91(2):243–258.

Immunopathology of the renal vascular lesion of progressive systemic sclerosis (scleroderma).

D Lapenas, G P Rodnan, T Cavallo
PMCID: PMC2018197  PMID: 645827

Abstract

Patients with progressive systemic sclerosis (PSS, scleroderma) exhibit a variety of immunologic abnormalities. To verify whether the renal vascular lesions of such patients might be mediated by an immunologic mechanism, kidney tissues of 16 patients with PSS were investigated by means of fluorescence, light, and electron microscopy; elution of tissue-bound antibody; and fixation of heterologous (guinea pig) complement. Controls consisted of 12 nonsclerodermatous patients with similar levels of hypertension with no evidence of associated immunologic abnormalities. Diffuse vascular deposits of immunoglobulins (predominantly IgM) and/or complement (predominantly Clq) were found in all 16 patients with PSS. These deposits were bound to the intima of intralobular and arcuate arteries which, by light microscopy, often exhibited typical fibromucinous alterations. Elution of antibody and heterologous complement fixation studies suggested that such reactants may represent the interaction of complement-fixing antibody and antigen. Electron microscopies studies demonstrated abundant fibrillar and ground substance material in the arterial intima but features of deposited (circulating) immune complexes were not found. By contrast, in the hypertensive (control) group, deposits of immunoglobulin (s) and/or complement were rare and, when present, were mostly confined to the arterioles. As judged by the results of elution and heterologous complement fixation, these arteriolar deposits appeared to represent trapped rather than specifically bound serum proteins. The possible signficance of these findings are discussed in relation to immunologic mechanisms which might be implicated in the pathogenesis of the renal vascular disease of PSS.

Full text

PDF
243

Images in this article

257Figure 1
on p.257
257Figure 2
on p.257
257Figure 3
on p.257
257Figure 4
on p.257
258Figure 5
on p.258
258Figure 6
on p.258

Selected References

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

  1. Alarcón-Segovia D., Fishbein E. Immunochemical characterization of the anti-RNA antibodies found in scleroderma and systemic lupus erythematosus. I. Differences in reactivity with Poly (U) and Poly-(A) Poly (U). J Immunol. 1975 Jul;115(1):28–31. [PubMed] [Google Scholar]
  2. Border W. A., Lehman D. H., Egan J. D., Sass H. J., Glode J. E., Wilson C. B. Antitubular basement-membrane antibodies in methicillin-associated interstitial nephritis. N Engl J Med. 1974 Aug 22;291(8):381–384. doi: 10.1056/NEJM197408222910803. [DOI] [PubMed] [Google Scholar]
  3. Campbell P. M., LeRoy E. C. Pathogenesis of systemic sclerosis: a vascular hypothesis. Semin Arthritis Rheum. 1975 May;4(4):351–368. doi: 10.1016/0049-0172(75)90017-7. [DOI] [PubMed] [Google Scholar]
  4. Cannon P. J., Hassar M., Case D. B., Casarella W. J., Sommers S. C., LeRoy E. C. The relationship of hypertension and renal failure in scleroderma (progressive systemic sclerosis) to structural and functional abnormalities of the renal cortical circulation. Medicine (Baltimore) 1974 Jan;53(1):1–46. doi: 10.1097/00005792-197401000-00001. [DOI] [PubMed] [Google Scholar]
  5. Churg J., Grishman E. Ultrastructure of immune deposits in renal glomeruli. Ann Intern Med. 1972 Mar;76(3):479–486. doi: 10.7326/0003-4819-76-3-479. [DOI] [PubMed] [Google Scholar]
  6. Clark J. A., Winkelmann R. K., Ward L. E. Serologic alterations in scleroderma and sclerodermatomyositis. Mayo Clin Proc. 1971 Feb;46(2):104–107. [PubMed] [Google Scholar]
  7. D'Angelo W. A., Fries J. F., Masi A. T., Shulman L. E. Pathologic observations in systemic sclerosis (scleroderma). A study of fifty-eight autopsy cases and fifty-eight matched controls. Am J Med. 1969 Mar;46(3):428–440. doi: 10.1016/0002-9343(69)90044-8. [DOI] [PubMed] [Google Scholar]
  8. Davis B. K., Cavallo T. Membranoproliferative glomerulonephritis. Localization of early components of complement in glomerular deposits. Am J Pathol. 1976 Aug;84(2):283–298. [PMC free article] [PubMed] [Google Scholar]
  9. FENNELL R. H., Jr, REDDY C. R., VAZQUEZ J. J. Progressive systemic sclerosis and malignant hypertension. Immunohistochemical study of renal lesions. Arch Pathol. 1961 Aug;72:209–215. [PubMed] [Google Scholar]
  10. FISHER E. R., RODNAN G. P. Pathologic observations concerning the kidney in progressive systemic sclerosis. AMA Arch Pathol. 1958 Jan;65(1):29–39. [PubMed] [Google Scholar]
  11. Gerber M. A. Immunohistochemical findings in the renal vascular lesions of progressive systemic sclerosis. Hum Pathol. 1975 May;6(3):343–347. doi: 10.1016/s0046-8177(75)80096-7. [DOI] [PubMed] [Google Scholar]
  12. Gerber M. A., Paronetto F. New patterns of immunoglobulin deposition in the lesions of malignant nephrosclerosis, with special reference to IgE. Am J Pathol. 1971 Dec;65(3):535–542. [PMC free article] [PubMed] [Google Scholar]
  13. HEPTINSTALL R. H. Malignant hypertension; a study of fifty-one cases. J Pathol Bacteriol. 1953 Apr;65(2):423–439. doi: 10.1002/path.1700650215. [DOI] [PubMed] [Google Scholar]
  14. KINCAID-SMITH P., McMICHAEL J., MURPHY E. A. The clinical course and pathology of hypertension with papilloedema (malignant hypertension). Q J Med. 1958 Jan;27(105):117–153. [PubMed] [Google Scholar]
  15. Kondo H., Rabin B. S., Rodnan G. P. Cutaneous antigen-stimulating lymphokine production by lymphocytes of patients with progressive systemic sclerosis (scleroderma). J Clin Invest. 1976 Dec;58(6):1388–1394. doi: 10.1172/JCI108594. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. LEVINE R. J., BOSHELL B. R. Renal involvement in progressive systemic sclerosis (scleroderma). Ann Intern Med. 1960 Mar;52:517–529. doi: 10.7326/0003-4819-52-3-517. [DOI] [PubMed] [Google Scholar]
  17. Lindqvist K. J., Osterland C. K. Human antibodies to vascular endothelium. Clin Exp Immunol. 1971 Dec;9(6):753–760. [PMC free article] [PubMed] [Google Scholar]
  18. McGiven A. R., De Boer W. G., Barnett A. J. Renal immune deposits in scleroderma. Pathology. 1971 Apr;3(2):145–150. doi: 10.3109/00313027109071334. [DOI] [PubMed] [Google Scholar]
  19. Norton W. L., Hurd E. R., Lewis D. C., Ziff M. Evidence of microvascular injury in scleroderma and systemic lupus erythematosus: quantitative study of the microvascular bed. J Lab Clin Med. 1968 Jun;71(6):919–933. [PubMed] [Google Scholar]
  20. Norton W. L., Nardo J. M. Vascular disease in progressive systemic sclerosis (scleroderma). Ann Intern Med. 1970 Aug;73(2):317–324. doi: 10.7326/0003-4819-73-2-317. [DOI] [PubMed] [Google Scholar]
  21. Oliver J. A., Cannon P. J. The kidney in scleroderma. Nephron. 1977;18(3):141–150. doi: 10.1159/000180805. [DOI] [PubMed] [Google Scholar]
  22. PARONETTO F. IMMUNOCYTOCHEMICAL OBSERVATIONS ON THE VASCULAR NECROSIS AND RENAL GLOMERULAR LESIONS OF MALIGNANT NEPHROSCLEROSIS. Am J Pathol. 1965 Jun;46:901–915. [PMC free article] [PubMed] [Google Scholar]
  23. Pardo V., Fisher E. R., Perez-Stable E., Rodnan G. P. Ultrastructural studies in hypertension. II. Renal vascular changes in progressive systemic sclerosis. Lab Invest. 1966 Sep;15(9):1434–1441. [PubMed] [Google Scholar]
  24. RODNAN G. P., SCHREINER G. E., BLACK R. L. Renal involvement in progressive systemic sclerosis (generalized scleroderma). Am J Med. 1957 Sep;23(3):445–462. doi: 10.1016/0002-9343(57)90324-8. [DOI] [PubMed] [Google Scholar]
  25. Scott D. G., Rowell N. R. Immunohistological studies of the kidney in systemic lupus erythematosus and systemic sclerosis using antisera to IgG, C3, fibrin, and human renal glomeruli. Ann Rheum Dis. 1974 Sep;33(5):473–481. doi: 10.1136/ard.33.5.473. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Sinclair R. A., Antonovych T. T., Mostofi F. K. Renal proliferative arteriopathies and associated glomerular changes: a light and electron microscopic study. Hum Pathol. 1976 Sep;7(5):565–588. doi: 10.1016/s0046-8177(76)80103-7. [DOI] [PubMed] [Google Scholar]
  27. Steffen C. Antigenicity and autoantigenicity of collagen. Ann N Y Acad Sci. 1965 Jun 30;124(2):570–585. doi: 10.1111/j.1749-6632.1965.tb18988.x. [DOI] [PubMed] [Google Scholar]
  28. Tolnai G., Sarkar K., Jaworski Z. F., Irvine A. H. Obliterative intimal fibrosis in kidneys of dialyzed patients. Can Med Assoc J. 1969 Jan 18;100(3):116–120. [PMC free article] [PubMed] [Google Scholar]
  29. Vidt D. G., Robertson A. L., Jr, Deodhar S. D. Renal changes in progressive systemic sclerosis. Report of five cases. Cleve Clin Q. 1971 Oct;38(4):141–152. doi: 10.3949/ccjm.38.4.141. [DOI] [PubMed] [Google Scholar]
  30. WINTERBAUER R. H. MULTIPLE TELANGIECTASIA, RAYNAUD'S PHENOMENON, SCLERODACTYLY, AND SUBCUTANIOUS CALCINOSIS: A SYNDROME MIMICKING HEREDITARY HEMORRHAGIC TELANGIECTASIA. Bull Johns Hopkins Hosp. 1964 Jun;114:361–383. [PubMed] [Google Scholar]

Articles from The American Journal of Pathology are provided here courtesy of American Society for Investigative Pathology

RESOURCES