Clinical and serological correlates of antinucleosome antibodies in South Africans with systemic lupus erythematosus

Antinucleosome antibodies (AnuA) are increasingly recognized as an important biomarker in the diagnosis and subset stratification of patients with systemic lupus erythematosus (SLE). The aim of the study was to determine the sensitivity, specificity, and clinico-serological correlates of AnuA in black South Africans with SLE. We performed a cross-sectional study of 86 SLE patients attending a tertiary center and 87 control subjects. AnuA were tested using a second-generation enzyme-linked immunosorbent assay (ELISA). The sensitivity, specificity, positive predictive value, and negative predictive value of AnuA were 45.3, 94.3, 88.6, and 63.6%, respectively. The presence of AnuA were strongly associated with the co-presence of anti-dsDNA antibodies (OR = 3.4, p < 0.0005) and antihistone antibodies (OR = 15.7, p < 0.00001). Patients who were seropositive for AnuA were more likely to have skin involvement (discoid lupus and/or malar rash) and had higher SLE disease activity index (SLEDAI) scores and Systemic Lupus International Collaborative Clinics/American College of Rheumatology (SLICC/ACR) damage scores (p < 0.05). IgG anticardiolipin antibody (aCL) levels showed a significant correlation with AnuA ratios (p < 0.01). Our findings provide further evidence that AnuA are a sensitive and specific diagnostic biomarker in SLE. Moreover, our finding that the presence of AnuA, but not anti-dsDNA antibodies, are associated with worse SLICC/ACR damage scores suggest that AnuA may have a role in predicting disease outcome. The correlation between IgG aCL and AnuA is a novel finding that merits further studies to determine possible common peptide specificities of the antibodies.     

Burden of comorbidities in South Africans with systemic lupus erythematosus

Clinical Rheumatology - To investigate the prevalence and spectrum of comorbidities in South Africans with systemic lupus erythematosus (SLE). A nested case-control study of a known alive group...     

Autoantibodies in black South Africans with systemic lupus erythematosus: Spectrum and clinical associations

Summary The clinical features and autoantibody profile of 111 black South Africans (103 females and 8 males) with systemic lupus erythematosus was retrospectively analysed. The mean age of the patients was 35.1 years and mean duration of disease 3.5 years. The commonest clinical and laboratory features noted were arthritis (62.2%), hypocomplementaemia (61.2%), haematological abnormalities (60.5%) and malar rash (55%). The serological abnormalities included antinuclear antibodies (98.2%), anti-dsDNA (66.2%), anti-Sm (44.2%), anti-RNP (65.5%), anti-Ro (60.5%), anti-La (28.4%) and rheumatoid factor (10.1%). Positive clinicoserological associations observed included: combination of anti-dsDNA antibodies and low C4 levels with renal disease; anti-dsDNA antibodies with cutaneous vasculitis; anti-Sm antibodies with psychosis; anti-RNP antibodies with Raynaud's phenomenon; anti-Ro antibodies with renal disease, psychosis and malar rash. Anti-La antibodies showed a weak negative association with serositis and Raynaud's phenomenon. Most of these clinical correlates are consistent with past studies. The high frequency of anti-Sm and anti-RNP antibodies is similar to the observations in African-Americans and Afro-Caribbeans.     

Autoantibodies in black South Africans with systemic lupus erythematosus: Spectrum and clinical associations

Summary The clinical features and autoantibody profile of 111 black South Africans (103 females and 8 males) with systemic lupus erythematosus were retrospectively analysed. The mean age of the patients was 35.1 years and mean duration of disease 3.5 years. The commonest clinical and laboratory features noted were arthritis (62.2%), hypocomplementaemia (61.2%), haematological abnormalities (60.5%) and malar rash (55%). The serological abnormalities included antinuclear antibodies (98.2%), anti-dsDNA (66.2%), anti-Sm (44.2%), anti-RNP (65.5%), anti-Ro (60.5%), anti-La (28.4%) and rheumatoid factor (10.1%). Positive clinicoserological associations observed included: combination of anti-dsDNA antibodies and low C4 levels with renal disease; anti-dsDNA antibodies with cutaneous vasculitis; anti-Sm antibodies with psychosis; anti-RNP antibodies with Raynaud's phenomenon; anti-Ro antibodies with renal disease, psychosis and malar rash. Anti-La antibodies showed a weak negative association with serositis and Raynaud's phenomenon. Most of these clinical correlates are consistent with past studies. The high frequency of anti-Sm and anti-RNP antibodies is similar to the observations in African-Americans and Afro-Caribbeans.     

Anti-lactoferrin antibodies in systemic lupus erythematosus: isotypes and clinical correlates

Lactoferrin (LF) is a multifunctional iron-binding protein present in several mucosal secretions as well as in secondary granules of polymorphonuclear leukocytes (PMN). Anti-LF antibodies, which belong to antineutrophil cytoplasmic antibodies (ANCA), have been described in several immunomediated diseases, including systemic lupus erythematosus (SLE), with conflicting results regarding either their prevalence or clinical associations. We studied the prevalence and isotype distribution of anti-LF and their association with clinical manifestations, disease activity, and other autoantibodies in 97 patients (83 women) affected by SLE. Anti-LF were detected by enzyme-linked immunosorbent assay. Disease activity was assessed using the Systemic Lupus Activity Measure (SLAM). Cutoff for antibody positivity was set at three standard deviations (SD) above the mean optical density obtained in sera from 34 healthy subjects. Positive sera were arbitrarily subdivided into low (from >3 to 5 SD), medium (from >5 to 10 SD), and high (>10 SD) positive. IgG, IgM, and IgA anti-LF were detected in 53, 18, and 14 patients, respectively. IgG1, IgG2, IgG3, and IgG4 anti-LF were demonstrated in 34, 10, 31, and 35 patients, respectively. IgG anti-LF at the medium/high level were found in 33 patients, correlated with disease activity (p=0.017), anti-dsDNA (0.04), and anticardiolipin antibodies (p=0.02) and were associated with Raynauds phenomenon (p=0.028), renal involvement (p=0.007), serositis (p=0.026), and history of thrombosis (p=0.006). Anti-LF of IgM, IgA, or IgG subclass isotypes showed no correlation with clinical and serological findings. Our results demonstrate that anti-LF are frequently present in patients affected by SLE. IgG anti-LF at the medium/high level are associated with some clinical manifestations and other autoantibodies. However, it remains to be established whether anti-LF play a specific pathogenic role.     

Causes and predictors of death in South Africans with systemic lupus erythematosus

OBJECTIVES: Little is known about the long-term outcome and mortality patterns in systemic lupus erythematosus (SLE) in sub-Saharan Africa. We undertook a retrospective study of SLE in mainly black, unemployed patients, seen at a tertiary institution in Soweto, South Africa, to determine the causes and predictors of death. METHODS: Demographic, clinical and laboratory data and outcome were extracted from the case records of patients attending the Lupus Clinic at Chris Hani Baragwanath Hospital. RESULTS: Of the 270 case records with a diagnosis of SLE, 226 met the American College of Rheumatology classification criteria for SLE. The female to male ratio was 18 : 1. The mean (s.d.) age at presentation was 34 (12.5) yrs. Arthritis, nephritis and neuropsychiatric disease had a cumulative frequency of 70.4, 43.8 and 15.9% of patients, respectively. During the course of a mean follow-up period of 54.9 months, 193 (85.3%) and 89 (39.3%) patients were treated with oral corticosteroids and immunosuppressive agents, respectively. There were 55 (24.5%) known deaths and 64 (28.6%) patients were lost to follow-up. The estimated 5 yr survival rates were between 57 and 72%, depending on whether the group of patients lost to follow-up was classified in the analysis as either alive or dead. Infection (32.7%) was the commonest cause of death followed by renal failure (16.4%). Univariate analysis revealed that nephritis, neuropsychiatric disease and hypocomplementaemia were associated with an increased mortality, but multivariate analysis showed nephritis as the only significant predictor of mortality. CONCLUSION: Our findings suggest that SLE in indigent South Africans not only carries a poorer prognosis but also the main cause of death, infection and renal failure differ from those reported recently in industrialized Western countries. Nephritis is common in our patients and is the only independent predictor of poor outcome.     

Spectrum of infections and outcome among hospitalized South Africans with systemic lupus erythematosus

Clinical Rheumatology - Our aim was to determine reasons for admission, the prevalence and spectrum of infections, and the outcomes in a multiethnic cohort of hospitalized systemic lupus...     

Prevalence of anti-protein S antibodies in patients with systemic lupus erythematosus

OBJECTIVE: To determine the prevalence of circulating anti-protein S (anti-PS) antibodies in association with PS deficiency in patients with systemic lupus erythematosus (SLE). METHODS: Plasma was obtained from blood samples collected from 27 patients with SLE (5 men, 22 women; mean +/- SD age 32 +/- 10 years). Anti-PS antibodies were detected by immunoblotting according to a previously described method. Levels of free and total PS antigen were measured by enzyme-linked immunosorbent assay. PS activity was assayed by a clotting method. Levels of C4b binding protein (C4bBP) were measured by latex immunoassay. RESULTS: Among 27 patients with SLE, 19 (70.4%) had PS activity, and 12 (44.4%) had PS free antigen below the lower limit established for a normal population (mean -2SD). There was good correlation between PS activity and levels of PS free antigen (r = 0.851, P < 0.001), PS total antigen (r = 0.743, P < 0.001), and C4bBP (r = 0.597, P = 0.001). Circulating anti-PS antibodies and antiphospholipid antibodies (aPL) (IgG type) were detected in 7 (25.9%) and 14 (51.9%) of the 27 patients with SLE, respectively. Only 1 patient (3.7%) had both anti-PS antibodies and aPL. PS activities in patients who were positive for anti-PS antibodies (mean 38.7%) tended to be lower than those in patients who were negative for anti-PS antibodies (mean 54.9%), but the difference was not statistically significant. CONCLUSION: Anti-PS antibodies, independently of aPL, may play a role in the occurrence of PS deficiency in some patients with SLE, with possible effects on the function of PS that do not change the levels of PS antigens.     

HLA class II antigens associated with systemic lupus erythematosus in black South Africans.

OBJECTIVE--To assess the associations of HLA class II antigens with systemic lupus erythematosus (SLE) in black South Africans. METHODS--HLA-DRB1 genotype frequencies assigned by polymerase chain reaction (PCR) amplification and sequence specific oligonucleotide probes were compared between 49 black SLE patients from Baragwanath Hospital and 87 ethnically matched controls. HLA-DQA1 and -DQB1 genotypes were also assigned in 45 of the SLE patients and 74 controls by PCR using sequence specific primers. RESULTS--HLA-DRB1*02 was increased in the patients compared with controls (odds ratio = 3.67; 95% confidence interval = 1.49 to 9.02; p < 0.005). HLA-DQB1*0201 was not associated with development of the disease itself, but was associated with the presence of Ro antibodies (p = 0.01). HLA-DRB1*03 was less strongly linked to DQB1*02 in this population than in white populations and was not associated with SLE. CONCLUSIONS--In black South Africans there is evidence for a locus on DR2 haplotypes contributing to SLE. Another gene, possibly HLA-DQB1*02, not linked to DR2 is involved in the subset of patients exhibiting Ro antibodies.     

Heart involvement in systemic lupus erythematosus, anti-phospholipid syndrome and neonatal lupus

Cardiac involvement is one of the main complications substantially contributing to the morbidity and mortality of patients suffering from systemic autoimmune diseases. All the anatomical heart structures can be affected, and multiple pathogenic mechanisms have been reported. Non-organ-specific autoantibodies have been implicated in immune complex formation and deposition as the initial triggers for inflammatory processes responsible for Libman-Sacks verrucous endocarditis, myocarditis and pericarditis. Anti-phospholipid antibodies have been associated with thrombotic events in coronary arteries, heart valve involvement and intra-myocardial vasculopathy in the context of primary and secondary anti-phospholipid syndrome. Antibodies-SSA/Ro and anti-SSB/La antigens play a major pathogenic role in affecting the heart conduction tissue leading to the electrocardiographic abnormalities of the neonatal lupus syndrome and have been closely associated with endocardial fibroelastosis.     

Pulmonary dysfunction in systemic lupus erythematosus and anti-phospholipid syndrome patients

OBJECTIVE: To assess and compare parameters of pulmonary function in systemic lupus erythematosus (SLE) and anti-phospholipid syndrome (APS) patients. METHODS: Consecutive patients (n = 74) who were free of respiratory symptoms were divided into four groups: 1) SLE (n = 23); 2) SLE with anti-phospholipid antibodies (aPL) (n = 18); 3) SLE with APS (n = 20); and 4) primary APS (PAPS) (n = 13). Pulmonary function testing, single breath diffusion capacity of carbon monoxide (DLCO/SB) and echocardiography studies were performed. Induced sputum cytology was analysed. RESULTS: Forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1), and DLCO were significantly reduced in SLE compared to PAPS patients (p = 0.039; p = 0.017; p = 0.029, respectively). Elevated pulmonary arterial pressure was observed in two patients with SLE and aPL and in two with SLE and APS. Lymphocyte and eosinophil counts in induced sputum showed no significant differences; however, a trend towards lower CD4 counts in SLE vs. PAPS was noted (p = 0.086), while in patients with both SLE and APS, a low CD4/CD8 ratio was seen. Patients with APS were older than patients without APS (47.12+/-14.86 vs. 34.29+/-12.6, p = 0.0001), while SLE patients were younger than PAPS patients (38.19+/-14.68 vs. 48.53+/-13.97, p = 0.023). CONCLUSION: Abnormal pulmonary functions tests were detected frequently in asymptomatic patients with SLE or PAPS. Although SLE patients were younger, pulmonary function was significantly more impaired in SLE as compared to PAPS patients.     

Ocular manifestations in Egyptian systemic lupus erythematosus patients and their relation with disease activity and anti-phospholipid antibodies

Aim of the work

To identify the ocular manifestations in Egyptian SLE patients and its relation with disease activity and antiphospholipid (aPL) antibodies.

Prevalence and clinical associations of anticardiolipin antibodies in systemic lupus erythematosus: A prospective study

Summary The main objectives of the present study were to determine the prevalence of IgG and IgM anticardiolipin antibody (aCL) isotypes in systemic lupus erythematosus (SLE) in order to analyze their possible association with the clinical manifestations of the disease. Clinical features of 64 consecutive and unselected SLE patients were prospectively studied. Sera from the same patients taken during each clinical manifestation were tested for the presence of aCL. The prevalence of aCL was 43.75% for the IgG isotype and 9.4% for the IgM isotype. A strong linkage between the presence of these antibodies and the occurrence of both thrombosis and abortions was found: a weaker association with neurological events and thrombocytopenia was also demonstrated. The titre of aCL appeared to be linked with the probability of having the clinical manifestations associated with these autoantibodies. Our results suggest that thrombosis and abortion, and possibly thrombocytopenia and central nervous system involvement, may be associated with the presence of aCL at the time when these clinical events develop in SLE patients.     

Prevalence and clinical significance of antiprothrombin antibodies in patients with systemic lupus erythematosus or with primary antiphospholipid syndrome

BACKGROUND AND OBJECTIVE: Antibodies to prothrombin (aII) have been identified in patients with antiphospholipid antibodies, but their clinical significance is not well known. The aim of our study was to investigate their prevalence and association with clinical manifestations of the antiphospholipid syndrome (APS) in patients with primary APS or with systemic lupus erythematosus (SLE). DESIGN AND METHODS: A series of 177 patients with autoimmune diseases was studied: 70 with primary APS and 107 with systemic lupus erythematosus. A control group of 87 healthy volunteers were included in the study. aII were investigated in sera by an ELISA, using human prothrombin as antigen fixed in irradiated polystyrene plates. RESULTS: aII prevalence in patients with autoimmune disease was 47% (57% and 40% in patients with primary APS or with SLE, respectively) significantly higher than in controls (5%) (p<0.0001). In the whole series, thrombotic events were more prevalent in patients with aII (45% vs 28%; p=0.02). Moreover, aII was found to be an independent risk factor for arterial thrombosis (OR=2.4; p=0. 04). Similarly, in patients with SLE, aII were associated with both arterial and venous thrombosis (35% vs 14%; p=0.01), although only IgG-aII (OR=3.7; p=0.01) had an independent value as risk factor for thrombosis. However, a relationship between aII and thrombosis was not found in primary APS. aII were associated with thrombocytopenia only in patients with primary APS (OR=6.7; p=0.007). INTERPRETATION AND CONCLUSIONS: aII seem to be a serological marker of thrombosis in autoimmune diseases, mainly in SLE patients and/or in the arterial territory.     

Antiphospholipid antibodies: clinical significance in systemic lupus erythematosus

A radioimmunoassay using cardiolipin as antigen and labelled SPA, anti-human IgG, anti-human IgM, anti-human IgA as second antibodies in detecting anti-cardiolipin antibody with the sera from 308 patients and 70 normal controls. Among them, 126 patients were of SLE, 27 systemic sclerosis, 40 rheumatoid arthritis, 40 Sj?gren syndrome, 26 other connective tissue diseases, 7 syphilis and 32 with obstetric complications. The positive rate of anticardiolipin antibody were 42.9% (SLE), 29.7% (PSS), 20% (RA), 15% (SS), 26.9% (CTD), 85.7% (syphilis), 3.1% (obstetric complication), 0% (NC). In SLE the anticardiolipin antibody were well correlated with thrombocytopenia, cerebral lupus, thrombosis of vein and spontaneous recurrent abortion. Lupus anticoagulant (APTT) was found in 21.3% of SLE and biological false positive of VDRL test in 4.8%. Both of them correlated with the anticardiolipin antibody detected by the radioimmunoassay. The authors concluded that antiphospholipid antibodies is a group of commonly seen antibodies, which may play a rule in the pathogenesis of SLE. Further study is progressing.     

Functional disability and health-related quality of life in South Africans with rheumatoid arthritis and systemic lupus erythematosus

There is a paucity of data on the impact of chronic rheumatic diseases on functional disability and overall health-related quality of life (HRQOL) in Africans. Materials and methods: We compared Black South Africans (BSA) with rheumatoid arthritis (RA) (n=50) and systemic lupus erythematosus (SLE) (n=50) to geographically and ethnically matched controls cared for at a tertiary care facility. The modified health assessment questionnaire (mHAQ) and Medical Outcome Study short-form 36 (SF-36) scores and indices of disease activity and organ damage were collected from each group. Results: Compared to the controls, both the RA and SLE groups fared significantly worse in respect of all the domains and summary scales of the SF-36. Compared to the SLE group, the RA group scored significantly worse with respect to the mHAQ disability index (mHAQ-DI), physical function and bodily pain (BP) SF-36 subscales, and SF-36 summary physical component score (SF-PCS). In the RA group, both the mHAQ-DI and SF-PCS correlated strongly (p<0.005) with the tender joint count, patient global assessment, 28-joint composite disease activity score, physician global assessment, and pain score. The SF-PCS showed only a weak inverse correlation with the swollen joint count (r=−0.29, p<0.05). In the SLE group, the systemic lupus erythematosus disease activity index correlated inversely best with the SF-36 general health subscale (r=−0.56, p<0.0001) and, to a lesser extent, with the mental health, BP, and vitality subscales, and SF-PCS and SF-mental component summary scores. Conclusion: Both RA and SLE have profound effects on HRQOL in BSA, with BP and physical disability particularly worse in RA patients. Disease activity, rather than organ damage or sociodemographic characteristics, correlates best with certain aspects of functional disability and HRQOL in both RA and SLE. Further longitudinal studies are needed to assess the clinical utility of measures of functional disability and HRQOL in this population.