New perspectives on the immunology of chronic mucocutaneous candidiasis

Chronic mucocutaneous candidiasis is a primary immune deficiency presenting as an inability to clear fungal infections and consequently as persisting and recurring infections of the skin and mucous membranes with yeasts, mostly Candida albicans. Chronic mucocutaneous candidiasis is a heterogeneous clinical syndrome which usually presents in childhood and can have an autosomal recessive, dominant or sporadic mode of inheritance. Most chronic mucocutaneous candidiasis patients also develop accompanying endocrine and inflammatory disorders that suggest an underlying deregulation of the immune system. It has long been recognized that protection from mucocutaneous candidiasis relies on cell-mediated immunity and studies on animal models have highlighted the essential role of type 1 cytokines in protection against Candida spp. Recent data in patients with chronic mucocutaneous candidiasis have documented altered patterns of cytokine production in response to Candida spp. with decreased production of some but not all type 1 cytokines and increased levels of interleukin-10. The defect underlying altered cytokine production remains unknown but studies are in progress addressing the putative role of dendritic cells and pattern recognition receptors in directing cytokine responses. These novel insights into immune mechanisms responsible for protection against Candida spp. are opening new possibilities of immunomodulation and vaccination that could prove beneficial in the management of chronic mucocutaneous candidiasis.     

Long-term follow-up and prognosis of chronic granulomatous disease in Yugoslavia: is there a role for early bone marrow transplantation?

We report the long-term follow-up of 12 pediatric-aged patients with chronic granulomatous disease (CGD). The mean age at the onset of infections was 5 months with a median delay in diagnosis of 2.5 years. Bacille Calmette–Guérin lymphadenitis was the most common presenting infection (6) followed by suppurative lymphadenitis (4), liver abscess (1), or Salmonella sepsis (1). Prophylaxis with cotrimoxazole was recommended to all patients. During the mean follow-up of 10 years (range, 4–23 years) pneumonitis was the most prevalent infection (91%) followed by lymphadenitis (83%), aphtous stomatitis (58%), and liver abscesses (25%). Seven (58%) patients developed chronic lung disease due to grossly delayed diagnosis (3) or poor compliance with antimicrobial prophylaxis (4). Five (41%) patients died during the second decade of life of aspergillosis (3) or chronic lung disease (2). Probability of survival into the third decade of life was estimated to be only 19%. We argue that HLA-identical bone marrow transplantation (BMT), if possible, should be attempted at early age because of significant morbidity and mortality in adolescence. BMT also should be considered in patients who suffer severe infections despite antimicrobial prophylaxis or patients with evidence of chronic lung disease. Possibility of elective BMT from unrelated donors remains to be carefully evaluated.     

Genotyping of Eight Human Platelet Antigen Systems in Serbian Blood Donors: Foundation for Platelet Apheresis Registry

IntroductionThe aim of this study was to investigate the allele and genotype frequencies of 8 human platelet antigen (HPA) systems among blood donors from the Blood Transfusion Institute of Serbia and to compare them with published studies. These data would be useful to establish the basis for a platelet apheresis donor registry.Material and MethodsSeventy-two unrelated male platelet apheresis/blood donors from Serbia were typed for 8 HPA systems (HPA-1 to HPA-6, HPA-9, and HPA-15) via the FluoGene method, based on polymerase chain reaction-sequence-specific amplification (PCR-SSP; PCR using sequence-specific primers) with fluorometric signal detection. Allele and genotype frequencies were estimated by direct counting and compared to the expected genotype frequencies according to the Hardy-Weinberg principle. The transfusion mismatch probability was calculated for every HPA specificity.ResultsThe allele frequencies were: HPA-1a, 0.868; HPA-1b, 0.132; HPA-2a, 0.917; HPA-2b, 0.083; HPA-3a, 0.611; HPA-3b, 0.389; HPA-5a, 0.903; HPA-5b, 0.097; HPA-9a, 0.993; HPA-9b, 0.007; HPA-15a, 0.472; and HPA-15b, 0.528. For HPA-4 and HPA-6 only allele a was detected.DiscussionThe HPA allele frequencies of European populations showed no significant differences in comparison with our results. Statistically significant differences were revealed in comparison with some populations of non-European origin. In the tested donors no HPA-2 bb genotype was detected, but we found 1 donor with the rare HPA-9b allele. The biggest transfusion mismatch probability in the Serbian population is for systems HPA-15 (37.4%) and HPA-3 (36.2%), which means that more than a third of random transfusions could cause mismatch in these systems. This study was enabled by the introduction of molecular HPA typing, and it provides initial results of the HPA allele and genotype frequencies in the population of blood donors in Serbia. They will be used to provide a compatible blood supply on demand for treating patients with alloimmune thrombocytopenic disorders. The successful implementation of PCR-SSP with fluorometric signal detection could be further complemented in the future by the introduction of high-throughput methods, which will largely depend on the available financial resources.