Reduced erythrocyte complement receptor type 1 in systemic lupus erythematosus is related to a disease activity index and not to the presence or severity of renal disease

Abstract

The present study investigated the expression of the complement receptor type 1 (CR1) on the membrane of erythrocytes (CR1/E) of patients with systemic lupus erythematosus (SLE) by flow cytometry. We found a significant reduction in CR1/E numbers in SLE patients (n ¹/4 52), compared to controls (512 + 171 and 689 + 146, respectively, P ¹/4 0.0001). Reduction was more pronounced in active disease patients. The mean CR1/E number observed in patients with inactive disease was 546 + 163 CR1/E, while active SLE patients presented a mean of 385 + 133 CR1/E(P ¹/4 0.001). Patients with SLE with similar activity indexes tend to have similar CR1/E numbers, irrespective of disease severity. We also observed a trend to CR1/E reduction in severe nephritis patients. A small group of SLE patients with chronic renal failure and inactive disease showed CR1/E numbers nearly identical to controls (689 + 146 versus 686 + 123, respectively, P ¹/4 0.95). This was the only group of SLE patients with normal CR1/E numbers. These results confirm the CR1/E reduction in SLE patients as previously described, and also suggest that this reduction is related to disease activity and not to disease severity.

Keywords

complement receptor complement system CR1 systemic lupus erythematosus

Get full access to this article

View all access options for this article.

References

Weisman HF , Bartow T , Leppo MK. Soluble human complement receptor type 1 in vivo inhibition of suppressing post-ischemic myocardial inflammation and necrosis . Science 1990; 249: 146-151 .

Hebert L , Cosio FG , Birmingham J , Mahan JD. Biologic significance of the erythrocyte complement receptor: A primate perquisite . J Lab Clin Med 1991; 118: 301-308 .

Ross GD , Lambris JD , Cain JA , Newman SL. Generation of three different fragments of bound C3 with purified factor I or serum. I. Requirements for factor H vs. CR1 cofactor activity . J Immunol 1982; 129: 2051-2060 .

Medof ME , Iida K , Mold C , Nussenzweig V. Unique role of the complement receptor CR1 in the degradation of C3b associated with immune complexes . J Exp Ed 1982; 156: 1739-1754 .

Lachmann PJ , Pangburn MK , Oldroyd RG. Breakdown of C3 after complement activation. Identification of a new fragment C3g, using monoclonal antibodies . J Exp Med 1982; 156: 205-216 .

Cornacoff JB , Herbert LA , Smead WA , Van Aman ME , Birmingham DJ , Waxman FJ. Primate erythrocyte immune-complex clearing mechanism . J Clin Invest 1983; 71: 236-247 .

Birmingham DJ , Hebert LA. CR1 and CR1-like: the primate immune adherence receptors . Immunol Rev 2001; 180: 100-111 .

Waxman FJ , Herbert LA , Cornacoff JB et al. Complement depletion accelerates the clearance of immune complexes from the circulation of primates . J Clin Invest 1984; 74: 1329-1340 .

Wong WW , Wilson JG , Fearon DT. Genetic regulation of a structural polymorphism of human C3b receptor . J Clin Invest 1983; 72: 685-693 .

10.

Walport MJ , Ross GD , Mackworth-Young C , Watson JV , Hogg N , Lachmann PJ. Family studies of erythrocyte complement receptor type 1 levels. Reduced levels in patients with SLE are acquired, not inherited . Clin Exp Immunol 1985; 59: 547-554 .

11.

Moldenhauer F , David J , Fielder AHL , Lachmann PJ , Walport MJ. Inherited deficiency of erythrocyte complement receptor type 1 does not cause susceptibility to systemic lupus erythematosus . Arthritis Rheum 1987; 30: 961-966 .

12.

Wilson JG , Wong WW , Murphy EE , Schur PH , Fearon DT. Deficiency of the C3b/C4b receptor of erythrocytes in systemic lupus erythematosus: analysis of the stability of the defect and of a restriction fragment length polymorphism of the CR1 gene . J Immunol 1987; 138: 2706-2710 .

13.

Krych-Goldberg M , Atkinson JP. Structure-function relationships of complement receptor type 1 . Immunol Rev 2001; 180: 112-122 .

14.

Chevalier J , Kazatchkine MD. Distribution in clusters of complement receptor type one (CR1) on human erythrocytes . J Immunol 1989; 142: 2031-2036 .

15.

Yoon SH , Fearon DT. Characterization of a soluble form of the C3b/C4b receptor (CR1) in plasma . J Immunol 1985; 134: 3332-3339 .

16.

Miyakawa Y , Yamada A , Kosaka K , Tsuda F , Kosugi E , Mayumi M. Defective immune-adherence (C3b) receptor on erythrocytes from patients with systemic lupus erythematosus . Lancet 1981; 2: 493-497 .

17.

Lida K , Mornaghi R , Nussenzweig V. Complement receptor (CR1) deficiency in erythrocytes from patients with systemic lupus erythematosus . J Exp Med 1982; 155: 1427-1438 .

18.

Wilson JG , Wong WW , Schur PH , Fearon DT. Mode of inheritance of decreased C3b receptors on erythrocytes of patients with systemic lupus erythematosus . N Engl J Med 1982; 307: 981-986 .

19.

Ross GD , Yount WJ , Walport MJ et al. Disease-associated loss of erythrocyte complement receptors (CR1, C3b receptors) in patients with systemic lupus erythematosus and other diseases involving autoanti-bodies and/or complement activation . J Immunol 1985; 135: 2005-2014 .

20.

Holme E , Fyfe A , Zoma A , Veitch J , Hunter J , Whaley K. Decreased C3b receptors (CR1) on erythrocytes from patients with systemic lupus erythematosus . Clin Exp Immunol 1986; 63: 41-48 .

21.

Mitchell JA , Batchelor JR , Chapel H , Spiers CN , Sim E. Erythrocyte complement receptor type 1 (CR1) expression and circulating immune complex (CIC) levels in hydralazine-induced SLE . Clin Exp Immunol 1987; 68: 446-456 .

22.

Tausk F , Harpster E , Gigli I. The expression of C3b receptors in the differentiation of discoid lupus erythematosus and systemic lupus erythematosus . Arthritis Rheum 1990; 33: 888-892 .

23.

Satoh H , Yokota E , Topkiyama K , Kawaguchi T , Niho Y. Distribution of the Hind III restriction fragment length polymorphism among patients with systemic lupus erythematosus with different concentrations of CR1 . Annals Rheum Dis 1991; 50: 765-768 .

24.

Kiss E , Csipo I , Cohen JH , Reveil B , Kavai M , Szegedi G. CR1 density polymorphism and expression on erythrocytes of patients with systemic lupus erythematosus . Autoimmunity 1996; 25: 53-58 .

25.

Cohen JH , Caudwell V , Levi-Strauss M , Bourgeois P , Kazatchkine MD. Genetic analysis of CR1 expression on erythrocytes of patients with systemic lupus erythematosus . Arthritis Rheum 1989; 32: 393-397 .

26.

Schur PH. Complement and systemic lupus erythematosus. In Wallace DJ , Hahn BH eds. Dubois’ systemic lupus erythematosus. Philadelphia: Lea & Febinger , 1993; 120-127.

27.

Tan EM , Cohen AS , Fries JF et al. The 1982 revised criteria for the classification of SLE . Arthritis Rheum 1982; 25: 1271-1271 .

28.

Bombardier C , Glandman DD , Urowitz M , Caron D , Chang CH and the Committee on Prognostic Studies in SLE . Derivation of the SLEDAI - A disease activity index for lupus patients . Arthritis Rheum 1992; 35: 630-640 .

29.

Currie MS , Vala M , Pisetsky DS , Greenberg CS , Crawford J , Cohen HJ. Correlation between erythrocyte CR1 reduction and other blood proteinase markers in patients with malignant and inflammatory disorders . Blood 1990; 75: 1699-1704 .

30.

Van Dyne S , Holers VM , Lublin DM , Atkinson JP. The polymorphism of the C3b/C4b receptor in the normal population and in patients with systemic lupus erythematosus . Clin Exp Immunol 1987; 68: 570-579 .