The clinical manifestations and response to treatment in South Africans with lupus nephritis.

There are varying observations on the influence of ethnicity on the clinical spectrum and response to treatment in lupus nephritis (LN). We studied a multiethnic South African LN cohort to determine the clinical manifestations, histological involvement and response to therapy. We reviewed the records of LN patients at Inkosi Albert Luthuli Central Hospital in Durban. There were 105 patients, 92.5% females and they comprised 49.1% Indians and 45.3% African Blacks. The mean age was 31.3 ± 12.5 years, and 41.5% had LN at first presentation of lupus. The most common histological classes were Class V alone in 34.9%, Class IV (± Class V) in 25.5% and Class III (±Class V) in 22.6%. The estimated glomerular filtration rate was reduced (<30 ml/min) at presentation in 15 (14.2%). Eighty-seven patients received therapy for LN. A response to induction therapy was noted in 81.6% and maintenance therapy (12 months) in 73.6%. Response to mycophenolate mofetil (MMF) was 80.4% and 68.4% during induction and maintenance therapy, respectively. There was no ethnic difference in the histological class or response to MMF but African Blacks had more severe renal disease at presentation. In conclusion, our multiethnic LN cohort shows a high prevalence of membranous LN and good response to treatment.

Comparison of ethnicity, gender, age of onset and outcome in South Africans with systemic lupus erythematosus.

Ethnicity, gender and age of onset are reported to influence the expression and outcome of systemic lupus erythematosus. We studied a multi-ethnic cohort of 408 South Africans (91.2% females) comprising 237 (58.1%) Indians, 137 (33.6%) African Blacks, 17 (4.2%) Mixed ethnicity and 17 (4.2%) Whites. The most common manifestations were arthritis (80.6%), photosensitivity (67.2%), oral ulcers (50.0%), malar rash (49.0%) and renal (39.2%). The common laboratory findings were positive anti-nuclear factor (96.8%), haematological (74.8%) and anti-dsDNA antibodies (45.3%). Serositis ( p = 0.002), nephritis ( p = 0.039), leucopaenia ( p = 0.001), haemolytic anaemia ( p = 0.026), anti-dsDNA antibodies ( p = 0.028) and anti-Sm antibodies ( p = 0.050) were more common in African Blacks compared to Indians. Males had increased prevalence of discoid rash ( p = 0.006) and anti-Sm antibodies ( p = 0.016). Discoid rash ( p = 0.018), renal involvement ( p < 0.001), psychosis ( p = 0.028), seizures ( p = 0.020), anti-dsDNA antibodies ( p = 0.009), leucopaenia ( p = 0.006), haemolytic anaemia ( p = 0.017) and thrombocytopaenia ( p = 0.023) were more common with early-onset systemic lupus erythematosus. On multivariate analysis, the independent predictors of death were renal involvement, anti-dsDNA antibodies and seizures. There were 53 (13%) deaths and the five- and 10-year survival was 90.8% and 85.7% respectively, with no differences related to ethnicity or age of onset. In conclusion, we report on the spectrum and outcome of systemic lupus erythematosus in a large South African multi-ethnic cohort.

CD43 interaction with ezrin-radixin-moesin (ERM) proteins regulates T-cell trafficking and CD43 phosphorylation.

Cell polarization is a key feature of cell motility, driving cell migration to tissues. CD43 is an abundantly expressed molecule on the T-cell surface that shows distinct localization to the migrating T-cell uropod and the distal pole complex (DPC) opposite the immunological synapse via association with the ezrin-radixin-moesin (ERM) family of actin regulatory proteins. CD43 regulates multiple T-cell functions, including T-cell activation, proliferation, apoptosis, and migration. We recently demonstrated that CD43 regulates T-cell trafficking through a phosphorylation site at Ser-76 (S76) within its cytoplasmic tail. Using a phosphorylation-specific antibody, we now find that CD43 phosphorylation at S76 is enhanced by migration signals. We further show that CD43 phosphorylation and normal T-cell trafficking depend on CD43 association with ERM proteins. Interestingly, mutation of S76 to mimic phosphorylation enhances T-cell migration and CD43 movement to the DPC while blocking ERM association, showing that CD43 movement can occur in the absence of ERM binding. We also find that protein kinase CΘ can phosphorylate CD43. These results show that while CD43 binding to ERM proteins is crucial for S76 phosphorylation, CD43 movement and regulation of T-cell migration can occur through an ERM-independent, phosphorylation-dependent mechanism.

Toxic psychosis due to chloroquine--not uncommon in children.

Toxic psychosis due to Chloroquine is a relatively uncommon occurrence in childhood. This entity must be kept in differential diagnosis in a case of unexplained psychosis, before resorting to a sophisticated array of detailed investigations. The purpose of this is to familiarize pediatricians with this relatively uncommon entity. The authors encountered four cases of psychosis with a wide variety of symptomatology over a period of the past 18 months.