Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0020639 (hypoproteinemia)
 1,134 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In order to examine the clinical characteristics and genetic background of secondary amyloidosis associated with rheumatoid arthritis, we analyzed clinical features and HLA typing of 85 patients in a multicenter study. Eighty-five patients with secondary amyloidosis associated RA were studied. The diagnosis of secondary amyloidosis were made on histological findings by biopsy or autopsy. The most common biopsy site was gastrointestinal tract (79.5%). Clinical symptom and the frequency at the time of diagnosis were; diarrhea (35 cases), abdominal pain (22 cases) and vomiting and nausea (16 cases). Abnormalities and the frequency in a laboratory test included proteinuria (49 cases), increased serum creatinine (32 cases), anemia (30 cases) and hematuria (15 cases). Twenty-eight patients were dead and 57 patients were alive at the time of the study. The average duration between diagnosis of amyloidosis and death was 19.4 +/- 18.5 (SD) months among the dead patients. The average duration after diagnosis of amyloidosis was 24.2 +/- 19.5 (SD) months in surviving patients. The causes of death were renal failure complicated with heart failure (6 patients), heart failure alone (3 patients) and renal failure alone (2 patients). Fifty-nine patients in the control group who were negative to amyloid deposition on biopsies at more than one site in the gastrointestinal tract, were clinically compared with patients in the amyloidosis group. No difference were noted in the age of RA occurrence and the stage between the two groups. As to the class, however, the number of patients with severe functional disorder (class 3 or severe) was larger in the amyloidosis group. There were no significant difference between the two groups in Lansbury's activity index. On hematology, biochemistry and urinalysis, the incidences of increased white blood cell count, anemia, increased platelet count, increased serum creatinine, hypoproteinemia, hypoalbuminemia, increased IgA, and increased urine and blood BMG were statistically significantly higher in the amyloidosis group than in the control group. HLA-A, -B, -C, and DR-locus antigens were compared in the 53 patients in the amyloidosis group and in the 59 subjects in the control group. There were no significant differences in frequency of HLA-A, and -B antigens between two groups. Frequency of CW7 antigen was significantly decreased in the amyloidosis group (13.2%) than in the control group (39.0%). Frequency of DR1 antigen was decreased in the amyloidosis group (3.8%) than in the control group (22.0%), although the difference was not significant. These findings suggest the possible involvement of genetic factors in the occurrence of amyloidosis. It is suggested that the occurrence of amyloidosis is suppressed by some genes which are linked with CW7 antigen.
 ...
PMID:[Clinical characteristics and genetic background of secondary amyloidosis associated with rheumatoid arthritis in Japanese]. 871 35

Two siblings, products of a consanguineous marriage, were markedly deficient in both albumin and IgG because of rapid degradation of these proteins, suggesting a lack of the neonatal Fc receptor, FcRn. FcRn is a heterodimeric receptor composed of a nonclassical MHC class I alpha-chain and beta(2)-microglobulin (beta(2)m) that binds two ligands, IgG and albumin, and extends the catabolic half-lives of both. Eight relatives of the siblings were moderately IgG-deficient. From sera archived for 35 years, we sequenced the two siblings' genes for the heterodimeric FcRn. We found that, although the alpha-chain gene sequences of the siblings were normal, the beta(2)m genes contained a single nucleotide transversion that would mutate a conserved alanine to proline at the midpoint of the signal sequence. Concentrations of soluble beta(2)m and HLA in the siblings' sera were <1% of normal. Transfection assays of beta(2)m-deficient cultured cells with beta(2)m cDNA indicated that the mutant beta(2)m supported <20% of normal expression of beta(2)m, MHC class I, and FcRn proteins. We concluded that a beta(2)m gene mutation underlies the hypercatabolism and reduced serum levels of albumin and IgG in the two siblings with familial hypercatabolic hypoproteinemia. This experiment of nature affirms our hypothesis that FcRn binds IgG and albumin, salvages both from a degradative fate, and maintains their physiologic concentrations.
 ...
PMID:Familial hypercatabolic hypoproteinemia caused by deficiency of the neonatal Fc receptor, FcRn, due to a mutant beta2-microglobulin gene. 2950 50