Immune Complexes, Complement, and Anti-DNA in Exacerbations of Systemic Lupus Erythematosus (SLE)

Lloyd, William E.; Schur, Peter H.

doi:10.1097/00005792-198105000-00004

Cited by 240 publications

(117 citation statements)

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“…Finally, there were no statistically significant differences in autoantibody profiles between female family members with and those without affected male relatives; however, the families with an affected male relative did show a trend (although not significant) toward abnormal CH50 results. Because abnormal CH50 levels are associated with a greater prevalence of renal disease (30,31), this trend further supports the notion of a disproportionate amount of renal dysfunction in families with affected male relatives.…”

Section: Discussionsupporting

confidence: 58%

Increased prevalence of renal disease in systemic lupus erythematosus families with affected male relatives

Stein

Olson

Gray‐McGuire

et al. 2002

Arthritis & Rheumatism

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Objective. To distinguish familial differences from sex-related differences in the clinical manifestations of systemic lupus erythematosus (SLE).Methods. A total of 372 affected individuals from 160 multiplex SLE pedigrees were analyzed. Twenty-five of these pedigrees contained at least 1 affected male relative. Comparisons of the presence of each of the 11 1982 American College of Rheumatology criteria for SLE were made between female family members with affected male relatives and those without affected male relatives, using Fisher's exact tests.Results. The presence of renal disease was significantly increased in female family members with an affected male relative when compared with those with no affected male relative (68% and 43%, respectively; P ‫؍‬ 0.002). This trend remained after stratifying by race and was most pronounced in European Americans. A familial basis for differences in hematologic and immunologic manifestations was also suggested, while arthritis and dermatologic features appeared to be most influenced by sex.Conclusion. Our results demonstrate that the increased prevalence of renal disease previously reported in men with SLE is, in large part, a familial rather than sex-based difference, at least in multiplex SLE families. Distinguishing familial from sex-related differences may facilitate efforts to understand the genetic and hormonal factors that underlie this complex autoimmune disease.

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Section: Discussionsupporting

confidence: 58%

Increased prevalence of renal disease in systemic lupus erythematosus families with affected male relatives

Stein

Olson

Gray‐McGuire

et al. 2002

Arthritis & Rheumatism

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“…Second, serum C3 and serum C4 have been widely used in attempts to monitor disease activity in SLE. Although the utility of these measurements is a subject of controversy, it is generally held that in some patients, particularly those with lupus nephritis, these are useful tests (3)(4)(5)10,13,14). Surprisingly, these tests have not been replaced or improved upon despite enormous advances in our understanding of complement biology during the last 20 years.…”

Section: Discussionmentioning

confidence: 99%

“…Although serum levels of C3, C4, and their activation-derived products are frequently used to monitor disease activity in SLE, their value as biomark-ers is a subject of controversy (3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13). These observations have led us to consider measurement of complement activation products bound to circulating blood cells (14,15).…”

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confidence: 99%

Reticulocytes bearing C4d as biomarkers of disease activity for systemic lupus erythematosus

Liu

Manzi

Kao

et al. 2005

Arthritis & Rheumatism

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Objective. There is an urgent need for biomarkers with which to monitor disease activity in patients with systemic lupus erythematosus (SLE). We recently showed that abnormal levels of C4d, an activationderived fragment of complement component C4, are deposited on the surface of erythrocytes from patients with SLE. This study focused on reticulocytes, the youngest and shortest-lived erythrocytes (lifespan 24-48 hours), with the objective of testing our hypothesis that when reticulocytes emerge from the bone marrow, they are immediately exposed to and acquire C4d at levels proportionate to the extent of complement activation at that time, thereby reflecting disease activity in SLE.Methods. We conducted a cross-sectional study of 156 patients with SLE, 140 patients with other diseases, and 159 healthy controls. Levels of C4d on the surface of reticulocytes were examined using a 2-color flow cytometric assay. The results were analyzed for correlations with SLE disease activity.Results. A wide range of increased levels of reticu-

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“…By contrast, only the occasional patient showed elevation of C3a anaphylatoxin levels, which in the group overall did not differ significantly from control values. Such potentially injurious activation of the classical pathway of the complement cascade is certainly what would be expected to result from the circulating pathogenic autoantibodies and immune complexes found in SLE (Lloyd & Schur, 1981) and it is, therefore, interesting to note some association of both elevated Clq binding activity and particularly DNA antibodies with the elevated C4a anaphylatoxin levels. The association of reduced C4 complement levels with elevated C4a anaphylatoxins is also very interesting, reflecting not only marked complement consumption but also, perhaps, the genetic predisposition to develop the disease, which is produced by complement deficiencies including C4 (Fielder et al, 1983).…”

Section: Dna-13mentioning

confidence: 99%

“…To date, no single immunological abnormality in SLE has proved to be a totally reliable indicator of active or aggressive disease (Lloyd & Schur, 1981;Valentijn et al, 1985). Neither DNA antibody assays (Davis, Percy & Russell, 1977;Bresnihan, 1979) nor total complement levels (Valentijn et cd., 1985;Morrow et al, 1982) have proved sensitive enough to be individually reliable, whilst tests for circulating immune complexes have quite often failed to correlate with active disease (Abrasera/., 1980; Inman era/., 1980), a tendency supported by the distribution of Clq binding activity in the present study.…”

Section: Dna-13mentioning

confidence: 99%

C4a anaphylatoxin levels as an indicator of disease activity in systemic lupus erythematosus

Wild

Watkins

Ward

et al. 1990

Clinical and Experimental Immunology

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SUMMARYThe use of a synthetic protease inhibitor, nafamstat mesilate, has enabled reliable estimations of in vivo complement activation to be made in systemic lupus erythematosus (SLE). Elevation of C3a anaphylatoxins was found in two out of 24 patients and elevation of C4a anaphylatoxins was found in 20 out of 24 patients, confirming that complement activation, predominantly by the classical pathway, is a common occurrence in the disease. Significantly higher levels of C4a anaphylatoxin were found in 16 patients, with more aggressive disease requiring supplementary treatment with azathioprine, while the remaining eight patients, with less severe disease, required purely steroid therapy. Very strong associations between elevated C4a anaphylatoxins and raised DNA antibody titres, Clq binding activity and low complement C4 levels were also observed, suggesting that anaphylatoxin measurement may be a sensitive additional method for monitoring disease activity in SLE.

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Immune Complexes, Complement, and Anti-DNA in Exacerbations of Systemic Lupus Erythematosus (SLE)

Cited by 240 publications

References 0 publications

Increased prevalence of renal disease in systemic lupus erythematosus families with affected male relatives

Increased prevalence of renal disease in systemic lupus erythematosus families with affected male relatives

Reticulocytes bearing C4d as biomarkers of disease activity for systemic lupus erythematosus

C4a anaphylatoxin levels as an indicator of disease activity in systemic lupus erythematosus

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