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Xanthomas are a common manifestation of lipid metabolism disorders. They include hyperlipemic xanthoma, normolipemic xanthoma, and a related condition, necrobiotic xanthogranuloma (NXG). All 3 forms can be associated with monoclonal immunoglobulin (MIg). In an attempt to improve diagnosis, understanding, and treatment of this association, we retrospectively analyzed a personal series of 24 patients (2 hyperlipemic xanthoma, 11 normolipemic xanthoma, and 11 NXG) and 230 well-documented reports from the literature. With the exception of the nodules and plaques featured in NXG, the clinical presentation of xanthomatous lesions usually resembled that seen in common hyperlipidemic forms and could not be used to suspect MIg-associated xanthomas. Extracutaneous sites were not rare. The MIg was an IgG in 80% of cases. Myeloma was diagnosed in 35%. Hypocomplementemia with low C4 fraction was present in 80% of studied patients. Low C1 inhibitor serum levels were found in 53%. Cryoglobulinemia was detected in 27%. These abnormalities suggest immune complex formation because of interactions between the MIg and lipoproteins and argue in favor of a causal link between MIg and xanthomas. Monoclonal gammopathy therapy could thus be an option. Indeed, among the patients who received chemotherapy, hematologic remission was accompanied by improvement in xanthoma lesions in several cases. [ABSTRACT FROM AUTHOR]

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]

Background. Strong T cell and antibody responses to human immunodeficiency virus (HIV), low virus production, and some genetic traits have been individually associated with nonprogression of HIV infection, but the best correlate with protection against disease progression remains unknown. Methods. We prospectively followed 66 untreated long-term nonprogressors and analyzed relationships between HIV-1-specific CD4 T helper (Th) 1 and CD8 T cell responses and HIV-1-specific antibodies, HIV-1 RNA and proviral DNA loads, host genes, and CD4 Thi cell counts at entry into the study and 4 years later. Results. HIV-1 p24-specific CD4 Thi cell proliferation, interferon (IFN)-γ production, and IFN-γ-producing cell frequencies at entry significantly and negatively correlated with HIV- 1 RNA and proviral DNA loads and were independent of CD4 Thi cell counts and host genes. HIV-1 Gag-specific IFN-γ-producing CD8 T cell frequencies correlated with HIV-1 proviral DNA loads but not with RNA loads. Only high frequencies of HIV-1 p24-specific CD4 Thi cells combined with HIV-1 gp41-specific IgG2 antibodies significantly predicted persistence of high CD4 Thi cell counts. Conclusion. HIV-1-specific CD4 Thi responses combined with IgG2 antibodies and IFN-γ-producing CD4 Thi cells are better predictors of long-term nonprogression than are virus parameters, host genes, or HIV-1-specific CD4 Thi or CD8 T cell proliferation. [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]

Study Objective: To determine whether zidovudine is effective in increasing the platelet count in patients with thrombocytopenic purpura related to human immunodeficiency virus (HIV) infection.Design: Nonrandomized controlled trial with two consecutive regimens.Setting: Immunopathology and hematology clinics at two general hospitals.Patients: Consecutive sample of 34 patients infected with HIV who had thrombocytopenic purpura (platelets less than 50 x 10(9)/L) without visceral bleeding. Twenty-nine patients completed the study; one patient was removed because of drug toxicity.Interventions: Zidovudine for 12 weeks, 250 mg every 6 hours orally in 10 patients; and 500 mg every 8 hours orally in 24 patients.Measurements and Main Results: Three of ten patients receiving 250 mg every 6 hours and 12 of 24 patients receiving 500 mg every 8 hours had a persistent increase in their platelet counts. In both groups the mean value of the platelet count increased significantly by week 12; from 28 x 10(9)/L +/- 12 (SD) to 57 x 10(9)/L +/- 36 in the first group and from 20 x 10(9)/L +/- 13 to 77 x 10(9)/L +/- 42 in the second group (P less than 0.05 and P less than 0.01, respectively).Conclusions: Zidovudine is effective on platelet counts in some patients with HIV-related thrombocytopenia. These results suggest that HIV itself may play a direct or indirect role in the pathogenesis of this disorder. [ABSTRACT FROM AUTHOR]

Presents information on a study which examined the antinuclear autoantibodies of several patients with chronic autoimmune disorder for lamins. Methodology of the study; Results and discussion.

Mutations of Fas or Fas ligand genes result in the autoimmune lymphoproliferative syndrome (ALPS) in humans. We report here a diffuse large B-cell non-Hodgkin's lymphoma occurring in a man with ALPS. Fas-mediated lymphocyte apoptosis was defective in vitro, owing to a mutation within the death domain of the Fas molecule. High-dose methotrexate and doxorubicin–based chemotherapy led to complete remission of lymphoma. [ABSTRACT FROM AUTHOR]

Presents a case report of a 43-year-old homosexual man with HIV infection. Admission to the hospital for fever, arthralgia, and a cervical mass; Examination revealing angiolymphoid hyperplasia and foci of Kaposi's sarcoma; Demonstration of seroconversion to positivity for human herpesvirus 8 (HHV-8); Methods; Results; Discussion.