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. 1973 Jul;52(7):1779–1787. doi: 10.1172/JCI107359

Evidence for Complement Activation via the Alternate Pathway in Skin Diseases I HERPES GESTATIONIS, SYSTEMIC LUPUS ERYTHEMATOSUS, AND BULLOUS PEMPHIGOID

Thomas T Provost 1,2,3, Thomas B Tomasi Jr 1,2,3
PMCID: PMC302453  PMID: 4352464

Abstract

A patient with herpes gestationis, 6 of 6 patients with bullous pemphigoid, and 5 of 25 patients with systemic lupus erythematosus were found to have properdin deposited along the skin basement membrane.

The patient with herpes gestationis demonstrated by immunofluorescence basement membrane deposition of C3 and C5 in the absence of C1q, immunoglobulins, and light chains. A second patient with herpes gestationis had C3 deposition with no demonstrable immunoglobulins or light chains. A thermolabile humoral factor(s) capable of depositing C3 (without C1q or C4) on normal skin basement membrane was found in the sera of both patients with herpes gestationis. No anti-basement membrane antibodies could be demonstrated in the sera of these patients.

The patients with systemic lupus erythematosus and bullous pemphigoid who manifested properdin deposition also showed skin basement membrane deposits of C1q, C4, C3, C5, and immunoglobulins. C3 proactivator (C3PA) was also found deposited along the skin basement membrane of three patients with systemic lupus erythematosus and all six bullous pemphigoid patients.

This study provides suggestive evidence that activation of complement is occurring via the alternate pathway in herpes gestationis. In systemic lupus erythematosus and bullous pemphigoid, both the classical (antibody) mediated activation of complement as well as the alternate pathway may be operative.

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Selected References

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

  1. Bienenstock J., Tomasi T. B., Jr Secretory gamma-A in normal urine. J Clin Invest. 1968 May;47(5):1162–1171. doi: 10.1172/JCI105805. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. CLARK H. F., SHEPARD C. C. A DIALYSIS TECHNIQUE FOR PREPARING FLUORESCENT ANTIBODY. Virology. 1963 Aug;20:642–644. doi: 10.1016/0042-6822(63)90292-7. [DOI] [PubMed] [Google Scholar]
  3. Ensky J., Hinz C. F., Jr, Todd E. W., Wedgwood R. J., Boyer J. T., Lepow I. H. Properties of highly purified human properdin. J Immunol. 1968 Jan;100(1):142–158. [PubMed] [Google Scholar]
  4. Gewurz H., Pickering R. J., Naff G., Snyderman R., Mergenhagen S. E., Good R. A. Decreased properdin activity in acute glomerulonephritis. Int Arch Allergy Appl Immunol. 1969;36(6):592–598. doi: 10.1159/000230780. [DOI] [PubMed] [Google Scholar]
  5. Goodkofsky I., Lepow I. H. Functional relationship of factor B in the properdin system to C3 proactivator of human serum. J Immunol. 1971 Oct;107(4):1200–1204. [PubMed] [Google Scholar]
  6. Götze O., Müller-Eberhard H. J. The C3-activator system: an alternate pathway of complement activation. J Exp Med. 1971 Sep 1;134(3 Pt 2):90s–108s. [PubMed] [Google Scholar]
  7. Ishizaka T., Sian C. M., Ishizaka K. Complement fixation by aggregated IgE through alternate pathway. J Immunol. 1972 Mar;108(3):848–851. [PubMed] [Google Scholar]
  8. Jordon R. E., Day N. K., Sams W. M., Jr, Good R. A. The complement system in bullous pemphigoid. I. Complement and component levels in sera and blister fluids. J Clin Invest. 1973 May;52(5):1207–1214. doi: 10.1172/JCI107288. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Kolodny R. C. Herpes gestationis. A new assessment of incidence, diagnosis, and fetal prognosis. Am J Obstet Gynecol. 1969 May 1;104(1):39–45. doi: 10.1016/s0002-9378(16)34138-2. [DOI] [PubMed] [Google Scholar]
  10. Lynch F. W., Albrecht R. J. Homonal factors in herpes gestationis. Arch Dermatol. 1966 Apr;93(4):446–447. [PubMed] [Google Scholar]
  11. Morgan J. K. Herpes gestationis influenced by an oral contraceptive. Br J Dermatol. 1968 Jul;80(7):456–458. doi: 10.1111/j.1365-2133.1968.tb11981.x. [DOI] [PubMed] [Google Scholar]
  12. Müller-Eberhard H. J., Götze O. C3 proactivator convertase and its mode of action. J Exp Med. 1972 Apr 1;135(4):1003–1008. doi: 10.1084/jem.135.4.1003. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Oliveira B., Osler A. G., Siraganian R. P., Sandberg A. L. The biologic activities of guinea pig antibodies. I. Separation of gamma1 and gamma2 immunoglobulins and their participation in allergic reactions of the immediate type. J Immunol. 1970 Feb;104(2):320–328. [PubMed] [Google Scholar]
  14. Osmundsen P. E. Herpes gestationis. Report on 5 cases. Dermatologica. 1966;132(5):393–399. [PubMed] [Google Scholar]
  15. PILLEMER L., BLUM L., LEPOW I. H., ROSS O. A., TODD E. W., WARDLAW A. C. The properdin system and immunity. I. Demonstration and isolation of a new serum protein, properdin, and its role in immune phenomena. Science. 1954 Aug 20;120(3112):279–285. doi: 10.1126/science.120.3112.279. [DOI] [PubMed] [Google Scholar]
  17. Pickering R. J., Herdman R. C., Michael A. F., Vernier R. L., Gewurz H., Fish A. J., Good R. A. Chronic glomerulonephritis associated with low serum complement activity (chronic hypocomplementemic glomerulonephritis). Medicine (Baltimore) 1970 May;49(3):207–226. doi: 10.1097/00005792-197005000-00002. [DOI] [PubMed] [Google Scholar]
  18. Rothfield N., Ross H. A., Minta J. O., Lepow I. H. Glomerular and dermal depostion of properdin in systemic lupus erythematosus. N Engl J Med. 1972 Oct 5;287(14):681–685. doi: 10.1056/NEJM197210052871402. [DOI] [PubMed] [Google Scholar]
  19. Sandberg A. L., Osler A. G., Shin H. S., Oliveira B. The biologic activities of guinea pig antibodies. II. Modes of complement interaction with gamma 1 and gamma 2-immunoglobulins. J Immunol. 1970 Feb;104(2):329–334. [PubMed] [Google Scholar]
  20. Thunold S., Abeyounis C. J., Milgrom F. Reactions in agarose gel between C1q and aggregated gamma globulin. J Immunol. 1970 Mar;104(3):685–690. [PubMed] [Google Scholar]
  21. Tourville D. R., Adler R. H., Bienenstock J., Tomasi T. B., Jr The human secretory immunoglobulin system: immunohistoligical localization of gamma A, secretory "piece," and lactoferrin in normal human tissues. J Exp Med. 1969 Feb 1;129(2):411–429. doi: 10.1084/jem.129.2.411. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Vallota E. H., Forristal J., Davis N. C., West C. D. The C3 nephritic factor and membranoproliferative nephritis: correlation of serum levels of the nephritic factor with C3 levels, with therapy, and with progression of the disease. J Pediatr. 1972 Jun;80(6):947–959. doi: 10.1016/s0022-3476(72)80006-4. [DOI] [PubMed] [Google Scholar]
  23. Vallota E. H., Forristal J., Spitzer R. E., Davis N. C., West C. D. Characteristics of a non-complement-dependent C3-reactive complex formed form factors in nephritic and normal serum. J Exp Med. 1970 Jun 1;131(6):1306–1324. doi: 10.1084/jem.131.6.1306. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Westberg N. G., Naff G. B., Boyer J. T., Michael A. F. Glomerular deposition of properdin in acute and chronic glomerulonephritis with hypocomplementemia. J Clin Invest. 1971 Mar;50(3):642–649. doi: 10.1172/JCI106534. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Yonemasu K., Stroud R. M. Clq: rapid purification method for preparation of monospecific antisera and for biochemical studies. J Immunol. 1971 Feb;106(2):304–313. [PubMed] [Google Scholar]
  26. van der Meer J. B. Granular deposits of immunoglobulins in the skin of patients with dermatitis herpetiformis. An immunofluorescent study. Br J Dermatol. 1969 Jul;81(7):493–503. doi: 10.1111/j.1365-2133.1969.tb16024.x. [DOI] [PubMed] [Google Scholar]

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