Pathogenesis
Aparna Palit, Arun C. Inamadar in Systemic Sclerosis, 2019
The poorly controlled complement activation in various vascular diseases has shown to promote EC damage and apoptosis, expression of vascular cell adhesion molecules, and amplification of local immune response. In patients with SSc, hypocomplementemia, and an increased complement activation has been associated with the clinical severity of the disease. The higher small vessel score of C4d is associated with an increased risk of unrecoverable renal function. Factor H (FH), a fluid-phase regulator of alternate pathway, regulates the complement activation to target only foreign agents or altered self-cells. In vitro studies have shown a defective capacity of FH to protect complement mediated cellular damage in patients with SSc. The impaired expression of another membrane-bound regulator, membrane regulator protein has been demonstrated in endothelium of lesioned and non-lesioned skin of patients with SSc suggesting defective endothelial protection.
Nephrology
Fazal-I-Akbar Danish in Essential Lists of Differential Diagnoses for MRCP with diagnostic hints, 2017
GN and hypocomplementaemia:1 Primary complement deficiency.2 Cryoglobulinaemia type 2.3 SLE.4 GN (poststreptococcal; mesangiocapillary).5 Endocarditis.6 Shunt nephritis.
Lupus Nephritis
Richard K. Burt, Alberto M. Marmont in Stem Cell Therapy for Autoimmune Disease, 2019
A major feature of SLE is the production of antibodies directed against components of the cell nucleus. Among these, the anti-nuclear antibody (ANA) is most characteristic and is positive in significant titer in virtually all patients with SLE.8 These antibodies bind DNA, RNA, nucleic proteins and protein-nucleic acid complexes. Two such antibodies appear to be virtually unique to lupus: anti-double stranded DNA (anti-dsDNA), which is associated with nephritis, and anti-Smith.9,10 Hypocomplementemia is found at presentation in more than 75% of untreated patients with lupus and is commonly associated with active renal disease.11
Systemic lupus erythematosus and risk of infection
Published in Expert Review of Clinical Immunology, 2020
Megan R.W. Barber, Ann E. Clarke
Susceptibility to infection is also driven by acquired immune dysregulation, with disease activity identified as an independent predictor of infection in multiple SLE cohorts [20,22,25,42]. Anti-double-stranded DNA antibody positivity, hypocomplementemia, and frequent flares are independent predictors of infection [43]. The pathophysiology is complex, and a wide array of mechanisms are involved. Disease activity can breakdown cutaneous and mucosal barriers allowing microbial entry. Immune complex formation leads to hypocomplementemia which may inhibit the complement cascade. T helper cells have a diminished response to viral antigens, which is worsened by SLE disease activity [44]. Neutropenia and lymphopenia are also associated with disease activity and may increase infection rate [45].
A simultaneous presentation of drug-induced lupus with drug-induced ANCA vasculitis secondary to hydralazine use in a patient with sarcoidosis
Published in Baylor University Medical Center Proceedings, 2019
Maria Catalina Espinosa, Belicia Ding, Kati Choi, Daniel N. Cohen, Marco Marcelli, Onome Whiteru Ifoeze
Given similar features, it has been reported that DIL and ANCA DIV may represent one disease spectrum.2 Our patient demonstrated overlapping features of both drug-induced rheumatologic disorders. ANCA DIV was evidenced by extensive cutaneous leukocytoclastic vasculitis, positive ANCA, and anti-proteinase-3 antibody. DIL was manifested by oral ulcers, positive ANA and anti-histone antibody, thrombocytopenia, and hypocomplementemia. It has been reported that overlapping presentations of DIL with ANCA DIV have been characterized by the presence of high ANCA and ANA titers, positive anti-histone antibody, and positive anti-phospholipid antibodies, as seen in our patient. It has also been reported that such development of multiple antibodies may indicate a drug-induced autoimmune process. Hypocomplementemia has also been described, which was present in our case. Clinically these patients may present with small vessel vasculitis of the skin, as in our patient. Weight loss, cough, lung disease, and kidney disease have also been described.2
Immunophenotype involved in IgG4-related disease
Published in Modern Rheumatology, 2019
Satoshi Kubo, Shingo Nakayamada, Yoshiya Tanaka
In addition to basic research for IgG4-RD, there are hypothesis that cannot be explained theoretically in the clinical setting. In laboratory examinations, elevated serum IgG4, elevated IgE, hypocomplementemia, and low inflammatory response are generally seen in patients with IgG4-RD. However, the pathological significance of IgG4 in patients with IgG4-RD is not known, as mentioned earlier. IgG1 and IgG3 cause inflammation through complement activation and opsonization, while IgG4 lacks these functions. Furthermore, high level of IgG4 is sometimes seen even in patients who are in clinical remission. It is unknown whether IgG4 in IgG4-RD acts as an exacerbating factor. Meanwhile, since hypocomplementemia is seen as a result of the formation of strong immune complex, serious clinical conditions manifests in patients with hypocomplementemia. For example, activity of lupus nephritis is known to be strongly associated with hypocomplementemia. In contrast, there are no evidences of autoantibody production and involvement of immune complex in patients with IgG4-RD, although hypocomplementemia is seen. In order to resolve these clinical questions, there is need for the elucidation of the pathological processes that can offer a theoretical explanation of these phenomenon.
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