Factor H autoantibodies have been reported in approximately 10% of patients with atypical hemolytic uremic syndrome (aHUS) and are associated with deficiency of factor H-related proteins 1 and 3. In this study we examined the prevalence of factor H autoantibodies in the Newcastle cohort of aHUS patients, determined whether the presence of such autoantibodies is always associated with deficiency of factor H-related proteins 1 and 3, and examined whether such patients have additional susceptibility factors and/or mutations in the genes encoding complement regulator/activators. We screened 142 patients with aHUS and found factor H autoantibodies in 13 individuals (age 1-11 years). The presence of the autoantibodies was confirmed by Western blotting. By using multiplex ligation-dependent probe amplification we measured complement factor H-related (CFHR)1 and CFHR3 copy number. In 10 of the 13 patients there were 0 copies of CFHR1, and in 3 patients there were 2. In 3 of the patients with 0 copies of CFHR1 there was 1 copy of CFHR3, and these individuals exhibited a novel deletion incorporating CFHR1 and CFHR4. In 5 patients mutations were identified: 1 in CFH, 1 in CFI, 1 in CD46, and 2 in C3. The latter observation emphasizes that multiple concurrent factors may be necessary in individual patients for disease manifestation. (Blood. 2010;115:379-387)

In this study we have used multiplex ligation-dependent probe amplification (MLPA) to measure the copy number of CFHR3 and CFHR1 in DNA samples from 238 individuals from the UK and 439 individuals from the HGDP-CEPH Human Genome Diversity Cell Line Panel. We have then calculated the allele frequency and frequency of homozygosity for the copy number polymorphism represented by the CFHR3/CFHR1 deletion. There was a highly significant difference between geographical locations in both the allele frequency (X2 = 127.7, DF = 11, P-value = 4.97x10-22) and frequency of homozygosity (X2 = 142.3, DF = 22, P-value = 1.33x10-19). The highest frequency for the deleted allele (54.7%) was seen in DNA samples from Nigeria and the lowest (0%) in samples from South America and Japan. The observed frequencies in conjunction with the known association of the deletion with AMD, SLE and IgA nephropathy is in keeping with differences in the prevalence of these diseases in African and European Americans. This emphasises the importance of identifying copy number polymorphism in disease.

Leukocytes including monocyte/macrophages, granulocytes, and T lymphocytes were localized in the corpus luteum (CL) of pregnant and pseudopregnant rats using monoclonal antibodies reactive with lineage-specific antigens. Neutrophilic granulocytes and monocytes/macrophages were found to be the most abundant leukocyte populations in the CL during both pregnancy and pseudopregnancy. The density of neutrophilic granulocytes (MCA 149-reactive cells) increased approximately 2-fold after mating, to peak on Day 9 of pseudopregnancy (214 +/- 13 positive cells/0.125 mm2 grid area) and Day 10 of pregnancy (216 +/- 12/grid area), and then declined in later stages of CL life. In pregnant rats, monocytes/macrophages positive for the monoclonal antibody ED1 were most numerous during early CL life when they were approximately 6-fold more plentiful than at luteolysis (153 +/- 14/grid area at Day 5 vs. 25 +/- 2 at 2 days postpartum). In pseudopregnant rats, the density of ED1-positive cells declined approximately 5-fold during the life span of the CL (124 +/- 17/grid area at Day 2 vs. 20 +/- 2 at Day 13) prior to a second, somewhat lesser peak at luteal regression (84 +/- 12 at Day 15). Fewer monocyte/macrophages within the CL were found to express antigen reactive with the monoclonal antibody ED2, which is characteristically a marker for tissue-macrophages (7% of the density of ED1-positive cells at Day 5 in the pregnant group and 13% at Day 2 in the pseudopregnant group); and while there was an approximately 60% reduction in the number of ED2-positive cells during pregnancy, these cells were found not to fluctuate significantly in number over the course of CL life in pseudopregnant animals.(ABSTRACT TRUNCATED AT 250 WORDS)