Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0038002 (splenomegaly)
 9,873 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Enhanced gastrointestinal absorption of dietary substances is an important feature of normal neonatal life that also exists in particular disease states such as selective IgA deficiency and atopic allergy. In these studies, it is shown that patients with hypogammaglobulinemia have increased absorption of dietary bovine antigens and that most patients have large amounts of these proteins present in the serum even after an overnight fast. The amounts of such proteins were found to be correlated with spleen size and/or peripheral lymphoid hypertrophy. Interestingly, three patients with X-linked agammaglobulinemia did not have detectable amounts of these proteins in the serum nor did they have splenomegaly or lymphadenopathy. It is speculated that hypogammaglobulinemic patients have a specific gastrointestinal mucosal lesion that permits the chronic excessive absorption of dietary antigens and may result in lymphoid hypertrophy.
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PMID:Dietary protein antigenemia in humoral immunodeficiency. Correlation with splenomegaly. 619 9

Serum immunoreactive interleukin (IL-)1 alpha, IL-4, IL-6 and tumor necrosis factor (TNF) alpha were measured in 42 patients with primary hypogammaglobulinemia (25 common variable immunodeficiency (CVI), 10 congenital hypogammaglobulinemia (CH), 7 X-linked agammaglobulinemia (XLA), and in 21 healthy controls. The cytokine levels were correlated to other immunological parameters including serum levels of neopterin and soluble CD8 (sCD8) antigen. IL-6 was detectable in 48% and IL-4 in 36% of the CVI patients, but in none of the controls. Seventy-five percent of the CVI patients with elevated IL-4 levels had detectable IL-6. In contrast, no patients in the XLA group and only three CH patients had detectable IL-4 or IL-6 levels. TNF alpha and IL-1 alpha were detected in only a few serum samples with no significant differences between patients and controls. In the CVI group elevated IL-6 levels were significantly associated to reduced numbers of CD4+ and CD19+ lymphocytes, elevated levels of neopterin and sCD8 antigen, and occurrence of splenomegaly and bronchiectasis. The raised IL-6 levels were confirmed in longitudinal testing, probably reflecting a characteristic immunological dysregulation in these patients. Cytokine alterations may play a role in the pathogenesis of the immunodeficiency and for the clinical manifestations in CVI patients. Alternatively, elevated cytokine levels may be only a marker of chronic immune activation, particularly in monocytes, possibly delineating a distinct subgroup of patients within the heterogeneous CVI group.
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PMID:Elevated serum levels of interleukin-4 and interleukin-6 in patients with common variable immunodeficiency (CVI) are associated with chronic immune activation and low numbers of CD4+ lymphocytes. 790 14

Monocyte and macrophage dysfunction may be important for both immunopathogenesis and clinical manifestations in subgroups of patients with primary hypogammaglobulinaemia. In the present study we examined the ability to generate reactive oxygen species (ROS) in isolated monocytes from these patients by two different methods: superoxide dismutase (SOD) inhibitable cytochrome c reduction by O2- and nitroblue tetrazolium (NBT) reduction. Monocyte from patients with common variable immunodeficiency (CVI) demonstrated significantly enhanced ROS generation both unstimulated and stimulated (unopsonized zymosan and phorbol myristate acetate (PMA)). The enhanced oxidative burst response in CVI patients was found both with and without serum containing medium. Furthermore, serum from CVI patients did significantly enhance the oxidative burst response in monocytes from healthy blood donors compared with the effect of control serum. The enhanced ROS generation in CVI patients was significantly correlated with elevated serum levels of neopterin, reduced numbers of CD4+ lymphocytes in peripheral blood and occurrence of splenomegaly. In contrast to the CVI group, monocytes from patients with X-linked agammaglobulinaemia (XLA) did not show enhanced ROS generation. The increased oxidative burst response in monocytes from CVI patients most probably reflects in vivo activation of these cells. Our observations indicate the presence of a subgroup of CVI patients characterized by chronic immune activation particularly of monocytes. The enhanced ROS generation might be involved in immunopathogenesis (e.g. T cell dysfunction) and in the pathogenesis of clinical manifestations (e.g. malignancies and autoimmune disorders) in these patients.
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PMID:Enhanced generation of reactive oxygen species in monocytes from patients with common variable immunodeficiency. 805 Jan 70

Myeloid and plasmacytoid dendritic cells (MDCs, PDCs) play critical roles in B cell development and antibody production. Primary antibody deficiencies in humans might therefore reflect a deficit in MDCs and/or PDCs. We tested this hypothesis by measuring dendritic cell (DC) subset numbers in patients with common variable immunodeficiency (CVID), X-linked agammaglobulinaemia (XLA) and specific polysaccharide antibody deficiency (SPAD). In CVID both MDC and PDC numbers were markedly reduced. There was a graded reduction in all DC subsets across the Freiburg CVID groups (memory B cell classification) and the greatest deficit was seen in group Ia cases with the most severe disease. In contrast, MDC numbers alone were reduced in XLA whilst in SPAD the DC numbers were normal. In CVID, the number of MDCs correlated strongly with switched memory B cell percentage and total B cell count. Low numbers of DCs correlated with a greater incidence of autoimmunity, splenomegaly and granulomatous disease, and a higher incidence of clinical complications. Measurement of MDC and PDC numbers provides both prognostic information for clinical management and classification of CVID cases for future pathogenetic research. Our findings are consistent with the hypothesis that deficits in DC subsets are a critical feature in CVID.
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PMID:Selective deficits in blood dendritic cell subsets in common variable immunodeficiency and X-linked agammaglobulinaemia but not specific polysaccharide antibody deficiency. 1829 43