Fatal outcome in a patient with autoimmune hemolytic anemia associated with an IgM bithermic anti-ITP

BACKGROUND: Several cold autoantibodies (usually IgG) with IT specificity have been reported previously, as have autoantibodies with joint I and P blood group specificities (IP1, ITP1, iP1, IP). A fatal outcome associated with an IgM cold autoantibody of ITP specificity is reported. CASE REPORT: A 54-year-old man suffered from progressively severe cold autoimmune hemolytic anemia for 9 months. Hemoglobin concentration ranged from 6 to 7 g per dL (60-70 g/L) and reticulocytes from 3 to 5 percent (0.030-0.050). The direct antiglobulin test was weakly positive for IgM and strongly positive for C3d. The serum contained a cold agglutinin that reacted strongest with cord i red cells (RBCs) > adult I RBCs > adult i RBCs, which is consistent with IT specificity. The Donath-Landsteiner test was positive; the reaction was neutralized by globoside. The serum reacted weakly or was negative with RBCs from five group p blood donors, which suggests anti-ITP specificity. Dithiothreitol treatment of the serum abolished the cold agglutinin reactivity, which suggests that the anti-IT was IgM. The patient received > 40 RBC transfusions and failed to respond to oral steroids, oral cytoxan, high-dose pulse intravenous steroids, and plasma exchange at room temperature and at 35 degrees C. He died of sepsis following an unsuccessful trial of chlorambucil. Autopsy revealed unsuspected disseminated non-Hodgkin's lymphoma. CONCLUSION: Serologic studies are consistent with our patient's having a single IgM cold autoantibody with IT and P specificities (anti-ITP) and requiring both specificities on the same RBC to permit maximal antibody expression.     

Comprehensive association analyses of IGF1, ESR2, and CYP17 genes with adult height in Caucasians

Human adult height is closely related to body growth that is regulated by multiple cytokines or hormones like growth hormone (GH) and estrogen. Our study focused on three potential candidate genes to human height, namely IGF1 (insulin-like growth factor 1), ESR2, and CYP17. We genotyped 43 single nucleotide polymorphisms (SNPs) and tested their associations in 1873 subjects from 405 nuclear families, using both the family-based quantitative transmission disequilibrium test (QTDT) and population-based ANOVA methods. Both analyses consistently detected that two novel SNPs of IGF1, rs5742694 and rs2033178, were significantly associated with human height, with the P-values of 0.0097 and 0.0057 in QTDT analyses, 0.0002/0.004 (sample 1/sample 2) and 8.46 x 10(-5)/1.92 x 10(-5) in ANOVA analyses. For ESR2, significant associations were only detected in women (rs1256061: QTDT P=0.002, ANOVA P=0.002/0.012; rs17766755: QTDT P=0.019, ANOVA P=0.023/0.006; rs1256044: QTDT P=0.022, ANOVA P=0.002/0.034). Haplotype analyses corroborated our single-SNP results. However, no association was detected between CYP17 and human height. In conclusion, we identified the important effects of IGF1 and ESR2 on adult height variation in Caucasians, and first suggested the potential sex-specific effect of ESR2 on height variation in Caucasian women. It will be valuable for other independent studies to replicate and confirm these findings.