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Complement‐activation product C4d is deposited on normal erythrocytes, while abnormal levels have been observed on the surface of erythrocytes of patients with systemic lupus erythematosus (SLE). This study examines whether C4d also deposits on human platelet surfaces, and whether platelet‐bound C4d may provide a biomarker for SLE. We conducted a cross‐sectional study of 105 patients with SLE, 115 patients with other diseases, and 100 healthy controls. Levels of C4d on the surface of platelets were examined by flow cytometry and scanning confocal microscopy. Statistical analyses were performed to determine the clinical variables associated with platelet C4d.Abnormal levels of platelet C4d were found to be highly specific for SLE. Platelet C4d was detected in 18% of patients with SLE, being 100% specific for a diagnosis of SLE compared with healthy controls and 98% specific for SLE compared with patients with other diseases (P < 0.0001). In addition, platelet C4d was significantly associated with positivity for lupus anticoagulant (P < 0.0001) and anticardiolipin antibodies of the IgG (P = 0.035) or the IgM (P = 0.016) isotype. Platelet C4d was also significantly associated with SLE disease activity according to the SLE Disease Activity Index (P = 0.039), low serum C4 (P = 0.046), an elevated erythrocyte sedimentation rate (P = 0.006), and abnormal levels of C4d on erythrocytes (P < 0.0001).This observation suggests that platelet‐bound C4d may be a useful biomarker for SLE and may be a clue to the pathogenic mechanisms responsible for the myriad thrombotic and vascular complications of lupus associated with antiphospholipid antibodies. [ABSTRACT FROM AUTHOR]

C4?derived activation fragments are the only complement ligands present on the surfaces of normal erythrocytes. The significance of this observation is unknown, and the role of erythrocyte?bound C4 (E?C4) in human disease has not been explored. More than any other human disease, the pathogenesis of systemic lupus erythematosus (SLE) has been characterized by defects in clearance of complement?bearing immune complexes via erythrocytes expressing complement receptor 1 (CR1). This study was undertaken to determine whether these functional defects might be reflected by abnormal patterns of E?C4 and E?CR1 expression on erythrocytes of patients with SLE.We conducted a cross?sectional study of 100 patients with SLE, 133 patients with other diseases, and 84 healthy controls. Erythrocytes were characterized by indirect immunofluorescence and by flow cytometry for determination of levels of C4d and CR1.Patients with SLE had higher levels of E?C4d and lower levels of E?CR1 than did patients with other diseases (P ? 0.001) or healthy controls (P ? 0.001). The test was 81% sensitive and 91% specific for SLE versus healthy controls and 72% sensitive and 79% specific for SLE versus other diseases, and it had an overall negative predictive value of 92%.This is the first report of abnormal levels of E?C4d in human disease. We found that abnormally high levels of E?C4d and low levels of E?CR1 are characteristic of SLE, and combined measurement of the 2 molecules has high diagnostic sensitivity and specificity for lupus. Determination of E?C4d/E?CR1 levels may be a useful addition to current tests and criteria for SLE diagnosis. [ABSTRACT FROM AUTHOR]

To determine the long-term outcome and associated clinical, serologic, and pathologic features in a cohort of patients with connective tissue disease (CTD) and the anti–signal recognition particle (anti-SRP) autoantibody. Sera and clinical data were collected prospectively from consecutive adult patients with polymyositis (PM; n = 134), dermatomyositis (n = 129), or other CTDs (predominantly systemic sclerosis [SSc; n = 790]). Patients were first evaluated during 1973–2001. Nineteen patients with the anti-SRP autoantibody were identified, 16 (84%) of whom had pure PM and 3 (2 with SSc and 1 with antisynthetase syndrome) had yet to develop features of myositis after a mean followup of 4.5 years (range 2.5–6 years). More SRP-positive PM patients had severe proximal muscle weakness (50%) and muscle atrophy (67%) at initial presentation compared with antisynthetase-positive PM controls. Cardiac involvement occurred in only 2 of 16 SRP-positive PM patients (13%), and interstitial lung disease was noted in 3 of 13 SRP-positive PM patients (23%) and in the 3 SRP-positive nonmyositis patients. There was a relative lack of inflammation in muscle biopsy specimens from the SRP-positive PM cohort. Other autoantibodies in the SRP-positive patients included Ro/SSA (4 patients), Th/To (1 patient), and anti–PL-12 (1 patient). Survival in the SRP-positive PM patients was comparable with that seen in the cohort of SRP-negative PM patients. The anti-SRP autoantibody is not specific for PM. Severe muscle weakness and atrophy were prominent features in PM patients with anti-SRP. Cardiac involvement was less common and survival was better in patients with anti-SRP than has previously been reported. [ABSTRACT FROM AUTHOR]

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 activation‐derived 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.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.A wide range of increased levels of reticulocyte C4d was specifically detected in SLE patients. These levels fluctuated in SLE patients and correlated with clinical disease activity, as determined by the Safety of Estrogens in Lupus Erythematosus: National Assessment (SELENA) version of the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) and the Systemic Lupus Activity Measure (SLAM). Specifically, in cross‐sectional analyses, patients with reticulocyte C4d levels in the highest quartile compared with those in the lowest quartile had significantly higher SELENA–SLEDAI (P = 0.00002) and SLAM (P = 0.02) scores. Longitudinal observation demonstrated that the reticulocyte C4d levels changed in relation to the clinical course in individual patients.These findings support our hypothesis that C4d‐bearing reticulocytes may serve as biomarkers of disease activity in patients with SLE. [ABSTRACT FROM AUTHOR]