Search

Background. The demonstration of in vitro cardiolipin reactivity with 2 human immunodeficiency virus (HIV)- specific, broadly neutralizing antibodies (2F5 and 4E10) has prompted reevaluation of autoimmune manifestations in HIV infection. Methods. We evaluated autoantibodies, particularly anticardiolipin (aCL), in 67 untreated, asymptomatic, HIVinfected individuals with slow progression of HIV disease and their correlation with 2F5-, 4E10-, b12-, and 2G12- like antibodies directed against epitopes involved in broad neutralization, as well as their correlation with immune activation and virological and clinical indicators. Fifty individuals with chronic HIV infection and standard disease progression were control patients. Results. The majority of the study patients with slow progression of HIV disease were men (78%); their median age was 37 years, their median CD4+ cell count was 672 cells/μL, and their median plasma HIV load was 6200 copies/mL. The majority of the control patients were also men (76%), and most (62%) were receiving highly active antiretroviral therapy; their median age was 43 years, their median CD4+ cell count was 202 cells/mL, and their median plasma HIV load was 2265 copies/mL. aCL immunoglobulin G was detected at similar levels in 49% of patients with slow progression of HIV disease and in 58% of control patients. Viral load was positively associated with aCL in both groups (P < .001), independent of CD4+ cell counts. In patients with slow progression of HIV disease, aCL levels were also correlated with plasma HIV load and cell-associated DNA level (r = 0.486 and r = 0.516, respectively; P < .001), with the proportion of activated CD4+ cells, human leukocyte antigen-DR+ cells (r = 0.445; P = < .001) but not activated CD8+ T cells, and with the level of B cell activation (quantified by soluble CD23; r = 0.354; P = .007). The level of aCL antibodies was associated with the level of antibodies to themembrane proximal region of gp41 (P = .003). Conclusion. aCL is frequently detected in HIV-infected patients, regardless of disease stage, and is strongly linked with the level of viral replication, the level of CD4+ T and B cell activation, and the level of antibodies to the membrane proximal external region of gp41, independent of CD4+ cell deficiency. [ABSTRACT FROM AUTHOR]

Marked polyclonal immunoglobulin (Ig)G4 hypergammaglobulinemia has exceptionally been reported. Here we report on two Algerian patients who presented a syndrome characterized by anemia, plasmacytic lymphadenopathy, renal manifestations, and a marked polyclonal IgG4 hypergammaglobulinemia leading to a hyperviscosity syndrome in one case. The IgG4-expressing cell percentage was significantly increased in the peripheral blood lymphocytes collected from the two patients upon diagnosis. Moreover, in contrast with normal sera, both patients’ sera significantly increased the percentage of IgG4-expressing cells when incubated with CD40-stimulated normal B lymphocytes. Similar effects were obtained with the culture supernatants of the patients’ activated T cells. Anti-interleukin (IL) 4 and/or anti-IL-13 antibodies were unable to antagonize the IgG4 production. IL-4 and IL-13 serum concentrations were found to be normal in the two patients. The increased IgG4 production was found to be mediated by soluble factor(s), most probably secreted by activated T cells, which did not require the signal transducer and activator of transcription 6 signaling pathway. [ABSTRACT FROM AUTHOR]

Abstract: Background: Antineutrophil cytoplasmic antibodies (ANCA) can be associated with various disorders. However, their association with neutropenia has never been reported. Methods: Nine patients with chronic unexplained neutropenia and ANCA were studied. Clinical charts were extensively analyzed and all patients underwent hematological and immunological investigations. Results: All patients (6 women and 3 men) were Caucasian and had a mean age of 49 years (range 16–67 years). All presented with a neutropenia below 1.5×109/L for more than 6 months. The neutropenia was <0.5×109/L in six cases and moderate in three. There was no evidence of toxic- or drug-related neutropenia or of a hematological malignancy. Autoimmune anemia and/or thrombocytopenia were present in five patients. ANCA, with various specificities, were present in all patients. ANCA were associated with various other autoantibodies in eight patients, including antisurface-neutrophil antibodies in three cases. Four of the six patients with severe neutropenia experienced infections. Five patients were treated with hematopoietic growth factors, steroids, intravenous immunoglobulins, splenectomy, methotrexate and/or cyclophosphamide, allowing the neutrophil count to be restored transiently or permanently. Conclusions: A subset of patients with neutropenia of possible autoimmune origin may develop ANCA. Their detection would provide strong evidence of an autoimmune mechanism. Neutropenia should be added to the list of ANCA-associated diseases. [Copyright &y& Elsevier]