Relationship between C4 null genes, HLA-D region antigens, and genetic susceptibility to systemic lupus erythematosus in Caucasian and Black Americans

Self Cite

176

Sdnuclear RNP were quantitated by enzyme-linked immunosorbent assay in 106 white patients with systemic lupus erythematosus. Two Ro autoantibody subgroups were identified that differed quantitatively, genetically, and clinically. The subgroup having anti-Ro only demonstrated significantly lower mean anti-Ro levels than did the subgroup with concomitant anti-La and showed a strong association with the linked HLA alleles DR2 and DQwl. The anti-Ro with anti-La sub- group was associated with the linked HLA alleles B8, DR3, DRw52, and DQw2 (DR3 was primary), and this subgroup consisted of patients with older ages at disease onset, sicca complex, and less renal involvement. Overall, the relative risk (RR) for having anti-Ro was highest in HLA-DR21DR3 heterozygotes compared with non-DR2/DR3 heterozygotes (RR 15) and all other DR combinations (RR 7), suggesting a compound effect of 2 immune responses. Heterozygotes for HLA-DQwl/ DQw2 demonstrated significantly higher mean levels of anti-Ro, which may be indicative of trans gene interaction at HLA-DQ. These data suggest the hypothesis that HLA genes exert their major effects on Ro/La autoantibody subsets of systemic lupus erythematosus.Genetic predisposition to systemic lupus erythematosus (SLE) has been associated with several alleles of the major histocompatibility complex (MHC). Those most consistently reported include HLA-B8, DR2, DR3, and DQwl, as well as null alleles of the HLA-linked second and fourth components of complement (1-8). When autoantibody subsets of SLE are considered, certain HLA antigen correlations become stronger. Most notably, in patients with SLE and in patients with other autoimmune diseases expressing anti-Ro and anti-La, HLA-DR3 andlor DR2 are found in the majority (4,5,9-13). Thus, MHC control of these immune responses, either qualitatively or quantitatively, has been suggested. Recently, enzyme-linked immunosorbent assays (ELISA) have been developed to measure anti-Ro, anti-La, and the anti-Sdnuclear RNP (anti-SmhRNP) complex (14)(15)(16)(17)(18)(19)(20). By virtue of being more sensitive and quantitative, these assays may provide greater insight into the role

Section: Resultssupporting

confidence: 76%

Two ro (ss‐a) autoantibody responses in systemic lupus erythematosus

Hamilton

Harley

Bias

et al. 1988

Self Cite

176

“…However, it should be noted that 2 erythrocyte blood group antigens, Rodgers and Chido, have been shown to correspond to the C4d region of C4A and C4B, respectively (16,28), suggesting that both C4A and C4B can bind to and persist on the surface membranes of normal erythrocytes. C4-null alleles or partial deficiency of C4A and/or C4B has been associated with human SLE (36)(37)(38)(39).…”

Section: Discussionmentioning

confidence: 99%

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

Liu

Manzi

Kao

et al. 2005

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-

“…In a number of recent studies, an increase in the frequency of C4A-null (C4A*pO) genes in Caucasian patients with SLE has been found (20,26,27,(32)(33)(34)(35)(36)(37)3942). Data from some of these studies are shown in Table 4.…”

Section: Discussionmentioning

confidence: 99%

“…Different investigators, including ourselves, have reported differing results, including increased frequencies of HLA-B8 (19,20), mozygous C4. and C4A and/or C4B deficiency (20,26, HLA-DR2 (3.…”

mentioning

confidence: 93%

The effect of ethnicity on major histocompatibility complex complement allotypes and extended haplotypes in patients with systemic lupus erythematosus

Schur¹,

Marcus-Bagley²,

Awdeh³

et al. 1990

Previous studies of patients with systemic lupus erythematosus (SLE) have shown an increased frequency of certain major histocompatibility complex (MHC) markers, including HLA-DR2, DR3, and C4AQO (CIA-null), -in Caucasian patients. However, most of these studies were of randomly selected, unrelated patients; families were not included, and haplotypes were not determined. In order to define more accurately the possible role of MHC genes in lupus susceptibility, HLA-A, B, C, and DR, as well as BF, C2, C4A, C4B, and GLO, markers were determined in 62 Caucasian patients of known ethnic background, and in the members of their families. The distributions of extended haplotypes (fixed combinations of HLA-B, DR, and complotype alleles), fragments thereof, and individual alleles were determined in SLE patients and controls. The MHC distributions in all patients were compared with haplotypes in a normal Caucasian population. There were no statistically significant differences between the frequencies of any MHC marker, fragment, or extended haplotype in the patients compared with the controls. The notion that genetic factors play a role in susceptibility to systemic lupus erythematosus (SLE) is based on the following observations: 1) there is a high rate of concordance for disease in monozygotic twins (14); 2) SLE and its immunologic abnormalities are found with increased frequency in relatives of SLE patients (5-11); 3) SLE is found more commonly in certain ethnic groups (12.13); and 4) a number of genetic markers have been found more frequently among SLE patients than in the general population. These genetic markers include the Gm phenotype 1.3.17:5.13.21 (14-16) and, according to some observers, low levels of erythrocyte CRl (17.18).