Familial lupus. family studies of hla and serologic findings

Abstract

HLA profiles in 103 members of 4 separate kindred with multiple occurrence of SLE were compatible with the presence of a disease susceptibility factor linked to HLA or a direct effect of antigens B8, A l l , and B35 on disease expression. Serum ANA was found in 52.9% of consanguineous, 56.5% of nonconsanguineous relatives of SLE probands, and 5% of controls, a finding that suggests the presence of a transmissible agent in the families. By contrast, lymphocytotoxic antibodies were not increased in relatives compared to controls.The familial occurrence in SLE is well documented and was recently reviewed (1).Both genetic and environmental factors have been implicated in the occurrence of SLE. The greater concordance for SLE in monozygous compared to dizygous twins (2) and the influence of genetic factors in the murine form of the disease (3) probands has been documented in several large studies (4-9) but no clear pattern of inheritance has been established. On the other hand, a high incidence of cold lyrnphocytotoxic antibodies in the consanguineous and nonconsanguineous relatives of SLE probands (10,ll) suggests a role for a transmissible agent in the occurrence of SLE.Although studies of HLA profiles in patients with sporadically occurring SLE have produced weak or negative associations with HLA antigens (12-17), the possibility of a lupus susceptibility factor linked to the major histocompatibility complex (M HC) has not been excluded. The present study was designed to determine whether the expression of disease among indentified family clusters of SLE was in any way related to the MHC. MATERIALS AND METHODSFamilies with multiple occurrence of SLE were selected for study. All available family members were interviewed by one of the authors and available medical records were reviewed. Tissue typing was performed on ficoll separated peripheral blood mononuclear cells (18) using UCLA Research Tray T8 (PI Terasaki, Department of Surgery, UCLA). Serum antinuclear antibody (ANA) was detected in sera routinely diluted 1 : 10 in saline using a standard immunofluorescent technique with peripheral blood leukocytes as substrate (19). Serum immunoglobulin (Ig) levels were quantitated using commercially available immunodiffusion plates (Kent Laboratories, Vancouver, British Columbia). Mean f 2 SD range was: IgG 710-1540 mg/dl, IgA 50-490 mg/dl, IgM

Familial Aggregation of Systemic Lupus Erythematosus and Coaggregation of Autoimmune Diseases in Affected Families

“…38 Genetic predisposition plays a crucial role in susceptibility, and environmental exposure can cause epigenetic change 39 or trigger activation of innate and adaptive immune response to induce or accelerate the development of SLE in susceptible individuals. 40 Strong familial aggregation in SLE has been reported [6][7][8][9][10][11][12][13][14][15][16] but, to the best of our knowledge, this is the first populationbased study investigating the familial aggregation of SLE and coaggregation of other autoimmune diseases in first-degree relatives of people with SLE. We found that the first-degree relatives have a 17-fold increased risk of SLE compared with the general population and that genetic relatedness is associated with the magnitude of risk of SLE.…”

“…3 Our group estimated that the prevalence of SLE was 0.10% in the United Kingdom 4 and 0.07% in Taiwan. 5 Early family studies [6][7][8][9][10][11][12][13] documented familial aggregation of SLE, and a classic twin study 14 found a 10-fold increased concordance in monozygotic compared with dizygotic twins. Furthermore, SLE has been reported 10,12 to coaggregate with other autoimmune diseases.…”

Familial rheumatoid arthritis: linkage of HLA to disease susceptibility locus in four families where proband presented with juvenile rheumatoid arthritis.

“…Recent reports associated Bw35 with necrotizing cutaneous venulitis (37), nonstreptococcal glomertulonephritis (38) and, in one family with inheritance of many of the clinical features of systemic lupus erythematosus (39). As Cleland et al (39) observed, the relationship of these diseases to HLA-Bwv35 is not clear.…”

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

“…However, there is an abundance of evidence to support the potential for a genetic contribution to the disease in these families, from both murine and human studies. Previous studies have examined familial aggregation of SLE in pedigrees containing affected male members (32)(33)(34). The report by Lahita et al (34) describes 4 unique pedigrees containing at least 2 affected male members each.…”