Complement System Protein C4 and Susceptibility to Hydralazine-Induced Systemic Lupus Erythematosus

Speirs, C. J.; Chapel, H M; Fielder, A. H. L.; Davey, Nick J.; Batchelor, J. R.

doi:10.1016/s0140-6736(89)92506-3

Cited by 78 publications

(41 citation statements)

References 15 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Another study showed a higher prevalence of complement C4 null alleles in patients with hydralazine DIL compared with the general population, implying higher lupus risk through activation of the classic complement pathway (93).…”

Section: Drugs Associated With Dilmentioning

confidence: 97%

Drug-Induced Glomerular Disease

Hogan

Markowitz²,

Radhakrishnan

2015

Clinical Journal of the American Society of Nephrology

View full text Add to dashboard Cite

Drug-induced autoimmune disease was initially described decades ago, with reports of vasculitis and a lupus-like syndrome in patients taking hydralazine, procainamide, and sulfadiazine. Over the years, multiple other agents have been linked to immune-mediated glomerular disease, often with associated autoantibody formation. Certain clinical and laboratory features may distinguish these entities from their idiopathic counterparts, and making this distinction is important in the diagnosis and management of these patients. Here, drug-induced, ANCA-associated vasculitis, drug-induced lupus, and drug-associated membranous nephropathy are reviewed.

show abstract

Section: Drugs Associated With Dilmentioning

confidence: 97%

Drug-Induced Glomerular Disease

Hogan

Markowitz²,

Radhakrishnan

2015

Clinical Journal of the American Society of Nephrology

View full text Add to dashboard Cite

show abstract

“…Within the DR4-positive populations, 9/9 PA patients, 19/41 normal controls and 15/24 cardiac Tx patients showed a DR4 association with DQw7. Table III shows that, when all individuals were considered, 16 There was a positive association of DQw7 and IgG antibody titers to total histones (x2 with Yates' correction = 3 .11; P fi 0.05; RR = 6.1 ) and H2A/H2B (x2 with Yates correction = 4.8, P 6 0.019; RR = 9.31). No association was found between DQw7 and urine 1&dquo;'igurre 1 Prevalence of HLA-DQw3 (hatched bars) and DQw7 (solid bars) in PA patients (n = 29), normal subjects (n = 153) and heart transplant (Tx) patients (n = 71).…”

Section: Mhc Antigensmentioning

confidence: 95%

Genetic, Immunologic and Biotransformation Studies of Patients on Procainamide

Adams

Balakrishnan

Roberts

et al. 1993

Lupus

View full text Add to dashboard Cite

This report represents follow-up observations of a unique long-term study of patients on procainamide (PA) for various cardiac arrhythmias. Serologic and clinical evaluations associated with drug-related autoimmunity were assessed and patients were characterized for factors postulated to influence susceptibility to autoimmunity, including acetylator phenotype, oxidative metabolism of PA, HLA class profile, and production of interleukin-1 (IL-1) and tumor necrosis factor (TNF). Fifty-two percent had IgM and 70% IgG antibodies to total histones; 67% had IgG antibodies to histone H2A/H2B. Patients were equally divided between fast and slow acetylators. N-oxidative metabolism of PA was indicated by the presence of urinary nitroprocainamide, which correlated with elevated titers of antihistone antibodies. There was a significant incidence of the DQw7 split of DQw3 in PA patients when compared to controls, and the frequency of antibodies to total histones and H2A/H2B was significantly increased in the DQw7 patients. C4A*QO and C4B*QO alleles were more frequent in the PA patients than in controls. IL-1 and TNF production was not different in patients compared to controls. These data suggest that certain genetic factors may serve as markers for PA-related autoimmunity.

show abstract

“…Although it is possible that confounding genes are hidden in these individuals, those who are deficient in C3 have a lower level of susceptibility to SLE compared with individuals who are deficient in C1 or C4, which are considered the major susceptibility factors. Genetic deficiencies in an individual locus are rare, but acquired deficiencies are possible, as a result for example, of drugs that inactivate C4 [103], or from the development of autoantibodies specific to C1q. Additional mechanisms can also lead to SLE.…”

Section: The Role Of C1q In Clearance Of Dying Cells and Slementioning

confidence: 99%

Clearance of dying cells and systemic lupus erythematosus: the role of C1q and the complement system

Mevorach

2010

Apoptosis

View full text Add to dashboard Cite

Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease of unknown etiology characterized by the presence of pathogenic high-titer autoantibodies to a diverse group of autoantigens. In 88% of patients, autoantibodies are present an average of 3.3 years before diagnosis. Antinuclear, anti-Ro, anti-La, and anti-phospholipid antibodies appear first, followed by anti-DNA, anti-Smith and anti-ribonucleoprotein. These autoantibodies have features of an antigen-driven, T-cell-dependent immune response. Once present, the course of SLE is characterized by disease flares and autoimmune dysregulation. Programmed cell death (PCD), an essential developmental and homeostatic mechanism, is the preferred physiological death processes for cells as well as an important immune response regulator. Appropriate clearance of apoptotic material completes the PCD process, and is essential for regulating of inflammation and maintaining self-tolerance. Early complement proteins are important in protecting humans against the development of SLE and the protective role of C1q and complement in SLE is mainly related to their role in clearance of dying cells. However, the complement system is also an important ingredient in inflammation, which mediates SLE pathogenesis. Thus, the question remains whether complement factors have either a protective or a destructive role, or a combination of both.

show abstract

Complement System Protein C4 and Susceptibility to Hydralazine-Induced Systemic Lupus Erythematosus

Cited by 78 publications

References 15 publications

Drug-Induced Glomerular Disease

Drug-Induced Glomerular Disease

Genetic, Immunologic and Biotransformation Studies of Patients on Procainamide

Clearance of dying cells and systemic lupus erythematosus: the role of C1q and the complement system

Contact Info

Product

Resources

About