ABSTRACT
Human parvovirus B19 (HPV) has been shown to be involved in the pathogenesis of various connective tissue and autoimmune diseases. In order to gain more information on HPV possible role in these diseases, we have investigated some immune responses in patients with acute HPV infection, mainly the secretion of the proinflammatory cytokine tumor necrosis factor (TNF)alpha and it's antagonist--the soluble TNF receptor (sTNFR) p75. Thirteen children with acute HPV infection and 13 healthy volunteers were investigated for the presence of autoantibodies, lymphocyte subpopulation counts, levels of total immunoglobulins, IgG subclasses and complement. The levels of TNFalpha and sTNFR p75 were determined in serum and conditioned medium (CM) from unstimulated and LPS stimulated peripheral blood mononuclear cell (PBMC) cultures. There was no difference between patients and controls regarding autoantibodies, lymphocytes, immunoglobulins, IgG subclasses and complement. A significant imbalance between TNFalpha and sTNFR p75 was found in the patients group. TNFalpha concentrations were significantly higher both in sera and in CM from the patients as compared with the controls. The levels of sTNFR concentrations were either similar (in sera) or significantly lower (in CM) in the patients compared with the controls. The TNF index, representing the biologically available TNFalpha, was significantly higher in patient's sera and CMs. In view of these results, it is conceivable that infection with human HPV in otherwise healthy children may lead to a proinflammatory state. The presence of high levels of biologically available TNFalpha, in susceptible individuals, may in turn play a role in the pathogenesis of systemic autoimmune diseases in HPV infected individuals.
Subject(s)
Antigens, CD/analysis , Parvoviridae Infections/immunology , Parvoviridae Infections/metabolism , Parvovirus B19, Human/immunology , Receptors, Tumor Necrosis Factor/analysis , Tumor Necrosis Factor-alpha/analysis , Tumor Necrosis Factor-alpha/metabolism , Acute Disease , Antigens, CD/blood , Autoimmune Diseases/immunology , Blood Cell Count , Cells, Cultured , Child , Culture Media, Conditioned/chemistry , Humans , Immunoglobulins/blood , Immunoglobulins/immunology , Lipopolysaccharides/pharmacology , Receptors, Tumor Necrosis Factor/blood , Receptors, Tumor Necrosis Factor, Type IIABSTRACT
BACKGROUND: Human parvovirus B19 is responsible for a variety of clinical syndromes, such as erythema infectiosum, non-immune hydrops fetalis, transient aplastic anemia, and arthropathies. HPV is also suspected of playing a role in the pathogenesis of various chronic inflammatory and autoimmune diseases, such as systemic lupus erythematosus, rheumatoid arthritis, Kawasaki disease and multiple sclerosis. OBJECTIVES: To study the age distribution and clinical presentation of patients hospitalized for human parvovirus B19 infection. METHOD: We reviewed the case records of all pediatric patients with serologic evidence of HPV infection who were admitted during a 20 month period to a major community hospital. RESULTS: Of 128 children tested for HPV, 48 had evidence of acute infection based on the presence of immunoglobulin M antibodies; 8 patients who also had positive IgM for other viruses were excluded, thus 40 case records were studied. The mean age of the patients was 5.21 years, but 22 patients were under 4. The clinical presentations included 25 patients with fever, either recurrent or prolonged, accompanied in some by enlarged spleen, liver and lymph nodes, skin rash and arthropathy; the remaining patients were investigated for anemia, skin rash, joint complaints and hepatitis. In addition, HPV infection was documented in several well-defined clinical conditions, such as SLE, vasculitic skin lesions, acute lymphoblastic leukemia, pure red cell aplasia, and optic neuritis. CONCLUSIONS: In a group of 40 pediatric patients exhibiting anti-HPV IgM antibodies, a younger age and less common clinical presentations were observed, furthermore 5 patients had clinical syndromes in which the causative role of HPV infection was not clear.
Subject(s)
Parvoviridae Infections/diagnosis , Parvovirus B19, Human , Acute Disease , Adolescent , Age Factors , Anemia/etiology , Antibodies, Viral/analysis , Child , Child, Preschool , Cohort Studies , Diagnosis, Differential , Erythema Infectiosum/diagnosis , Erythema Infectiosum/epidemiology , Exanthema/etiology , Female , Fever/etiology , Fluorescent Antibody Technique, Indirect , Hepatitis/etiology , Humans , Immunoglobulin M/analysis , Infant , Israel/epidemiology , Joint Diseases/etiology , Male , Optic Neuritis/etiology , Parvoviridae Infections/complications , Parvoviridae Infections/epidemiology , Parvovirus B19, Human/immunology , Seasons , Sex Factors , Syndrome , Time FactorsABSTRACT
The changes in cytokines and hormones involved in hematopoiesis were studied in the serum of 7 girls with anorexia nervosa, 15-24 yr old, on admission and after 5% and 10% weight gain. Hematopoiesis was studied by in-vitro culturing of circulating granulocyte-macrophage colony forming cells and erythroid burst forming cells. Nutritional status was studied by anthropometric measurements and resting energy expenditure. On admission, granulocyte-macrophage colony forming cells and erythroid burst forming cells were significantly lower than in age-matched controls and increased significantly along weight gain. Blood leptin and erythropoietin levels increased significantly with weight gain. TNF-alpha levels tended to decrease while IL-1beta levels were lower than in the controls on admission (p <0.05) and did not change significantly during weight gain. IL-3, GM-CSF and IL-6 were undetected on admission or along weight gain. The changes in granulocyte-macrophage colony forming cells and erythroid burst forming cells positively correlated with changes in resting energy expenditure and fat free mass. These results may suggest that undernutrition affects hematopoiesis as indicated by the reduction of hematopoietic progenitor cells before treatment and the significant increase with weight gain. The changes in the levels of hormones and cytokines known to be involved in hematopoiesis along refeeding may suggest a role for these factors in anorexia nervosa.