Association of Antibodies to Ribonucleoprotein and Sm Antigens with Mixed Connective-Tissue Disease, Systemic Lupus Erythematosus and Other Rheumatic Diseases

Fifty‐three patients (34 who had diffuse scleroderma, and 19 who had CREST syndrome [calcinosis, Raynaud's phenomenon, esophageal dysmotility, sclerodactyly, and telangiectasias]) were studied by noninvasive procedures, including resting electrocardiogram (ECG), continuous 24‐hour Holter ECG monitoring, M‐mode echocardiography, and 2‐dimensional echocardiography. Only 22 patients (42%) had abnormalities such as conduction defects, supraventricular or ventricular arrhythmias, or ST‐T changes detected on resting ECG. In contrast, using Holter monitoring, the number of conduction abnormalities seen increased from 10 to 16 patients and transient ST‐T changes increased from 2 to 18 patients. Forty‐eight patients had ventricular arrhythmias, with multiform ventricular premature beats in 21 (40%), pairs of runs of ventricular tachycardia in 15 patients (28%), and 1 or more runs of ventricular tachycardia in 7 (13%). Echocardiography detected asymmetric septal hypertrophy in 10 patients, impaired ventricular function in 9 patients, congestive cardiomyopathy in 2, mitral prolapse in 4, and pericardial effusion in 3 patients. Multiform and/or repetitive ventricular premature beats occurred more frequently in patients with echocardiographic abnormalities, but were also present in patients who had normal findings on echocardiographic examination. Cardiac involvement was not correlated with clinical variants of scleroderma (CREST syndrome or diffuse scleroderma), nor with other signs and symptoms of the disease. Thus, cardiac involvement is found much more frequently than would be expected from clinical symptoms or from results of resting ECG alone; therefore, Holter monitoring and echocardiography should be included in the routine workup of patients who have scleroderma.

Section: Methodsmentioning

confidence: 84%

Noninvasive evaluation of cardiac dysrhythmias, and their relationship with multisystemic symptoms, in progressive systemic sclerosis patients

Ferri

Bernini

Bongiorni

et al. 1985

“…To our knowledge, there has been no other example of autoantibodies in systemic autoimmune diseases that are associated with a "thromboprotective" role, although other autoantibodies with protective effects have been described (23). To date, aLB1 appear unique in this regard.…”

Section: Discussionmentioning

confidence: 96%

Association of autoantibodies to nuclear lamin B1 with thromboprotection in systemic lupus erythematosus: Lack of evidence for a direct role of lamin B1 in apoptotic blebs

Dieudé

Senécal

Rauch

et al. 2002

Objective. To demonstrate the association between autoantibodies to nuclear lamin B1 (aLB1) and protection against thrombosis ("thromboprotection") in patients with systemic lupus erythematosus (SLE), and to elucidate the mechanism by which aLB1 cause thromboprotection in vivo. Since a number of autoantigens in SLE have been localized specifically to the external surface of apoptotic blebs, it was hypothesized that circulating aLB1 may block the procoagulant effect of apoptotic blebs by binding to LB1 displayed at the external bleb surface.Methods. A cross-sectional study was performed using serum samples obtained at first evaluation of 259 English Canadian and French Canadian patients from SLE registries at 3 hospitals. A case-control study was performed to analyze the relationship between aLB1 and lupus anticoagulant (LAC) status and thrombotic manifestations between onset of disease and last followup. Reactivity of aLB1 with Jurkat or endothelial cells, which had been induced to undergo apoptosis, was determined by indirect immunofluorescence. Localization of LB1 in apoptotic cells and blebs was analyzed by confocal microscopy and surface labeling of cell membrane proteins.Results. High-titer aLB1 was restricted to a subset of SLE patients (46 patients), with an overall frequency of 17.8% (range 11.6-24.3% in the 3 centers). LB1 antibodies were significantly associated with LAC but not with antibodies to cardiolipin (aCL) or ␤ 2 -glycoprotein I (anti-␤ 2 GPI). The frequency of thrombosis differed markedly depending on aLB1 and LAC status, as follows: presence of LAC and absence of aLB1 50%, presence of both LAC and aLB1 22.7%, absence of both LAC and aLB1 25.5%, absence of LAC and presence of aLB1, 20.8%. Further subclassification of patients based on aCL and anti-␤ 2 GPI status revealed that, in the presence of LAC but in the absence of aCL, anti-␤ 2 GPI, and aLB1, the frequency of thrombosis was 40%, whereas in the presence of aLB1, it decreased strikingly, to 9.1%. LB1 was found to be translocated into surface membrane blebs during apoptosis and to be entirely enclosed within the apoptotic bleb plasma membrane of Jurkat and endothelial cells.Conclusion. The presence of aLB1 in SLE patients with LAC essentially nullifies the strong prothrombotic risk associated with LAC. Hence, aLB1 is associated with thromboprotection. Reactivity of aLB1 with apoptotic blebs does not seem to play a direct role in mediating this protection, since LB1 is buried within apoptotic blebs and inaccessible to circulating aLB1. The mechanism by which aLB1 confers thromboprotection in SLE remains to be elucidated.

“…This antibody is directed to the snRNA-containing ribonucleoprotein particles (snRNP), or more specifically to the 70-kd polypeptide uniquely present in the (U 1)snRNP complex (51,52). The antibody is not unique to MCTD; it can be found in patients with SLE and other connective tissue diseases (53)(54)(55). In 1 study, its presence failed to identify a particular subgroup within the overlap syndromes (3).…”

Section: Discussionmentioning

confidence: 99%

Hla type as a predictor of mixed connective tissue disease differentiation ten‐year clinical and immunogenetic followup of 46 patients

Gendi

Welsh

Venrooij

et al. 1995

Objective. To determine any clinical or genetic markers of differentiation and outcome in a previously described cohort of 46 patients with mixed connective tissue disease (MCTD).Methods. Patients were clinically evaluated, chart notes reviewed, and HLA subtyping and immunology profiles performed where possible. Eleven had died and 7 were lost to followup.Results. MCTD had differentiated into systemic lupus erythematosus in 12 patients and into systemic sclerosis in 13. The latter was associated with HLA-DR5 (P = 0.038), and nondifferentiation was associated with HLA-DR2 or DR4 (P = 0.007). Three HLA-DR4 positive patients had MCTD that evolved into rheumatoid arthritis. Erosive and/or deforming arthritis was associated with HLA-DR1 or DR4 (P = 0.015). HLA-DR3 was associated with interstitial lung fibrosis (P = 0.044) and keratoconjunctivitis sicca (0.001 < P < 0.01). Severe Raynaud's phenomenon predicted higher mortality (0.01 < P < 0.05). Conclusion.We suggest that MCTD is, for most patients, an intermediate stage in a genetically determined progression to a recognized connective tissue disease. Those whose disease remains undifferentiated might be considered a distinct subset.