B-lymphocyte subpopulations in patients with selective IgA deficiency.

INTRODUCTION: Selective deficiency IgA (IgAD) is the most common primary abnormality of immunoglobulin production with unknown pathophysiology. It is genetically related to common variable immunodeficiency (CVID), where besides IgA also IgG and frequently IgM serum levels are decreased. In this study we focused on determination of B-lymphocyte developmental stages and searching for similarities between CVID and IgAD. MATERIALS AND METHODS: Using flow cytometry we determined major lymphocyte subpopulations and B-lymphocyte subsets: naïve (CD27(-)IgD(+)), marginal zone cells (CD27(+)IgD(+)), class-switched memory cells (CD27(+)IgD(-)), "double-negative" B cells (CD27(-)IgD(-)), transitional cells (IgM(++)CD38(++)), plasmablasts (CD38(+++)IgM(+) or IgM(-)), and CD21(low)CD38(low) cells in 80 patients with IgAD, 48 patients with CVID, and 80 control persons. RESULTS: Compared to healthy controls, a decrease in the absolute number and frequency of CD4+ cells (both < 0.001) was observed in IgAD patients. A decrease in the frequency of switched memory cells (P < 0.001), transitional cells (P = 0.035) as well as plasmablasts (P < 0.001) and an increase in the CD21(low)CD38(low) subset (P = 0.007) was observed in IgAD patients compared to control persons. No significant differences were observed in the remaining B-cell developmental subsets. A decrease in CD27(+)IgD(-) (<0.4% of peripheral blood lymphocytes), frequently observed in CVID patients and also previously reported in IgAD, was found in only five patients (6%) with IgAD, two of them being first-degree relatives of CVID patients. CONCLUSION: Our results show a decrease of terminally differentiated B-lymphocyte subsets in patients with IgAD, similar as previously found in patients with CVID, but these results are less expressed than in CVID patients.

Change in referral diagnoses and diagnostic delay in hypogammaglobulinaemic patients during 28 years in a single referral centre.

BACKGROUND: The classical clinical manifestation of untreated immunoglobulin deficiency comprises predominantly recurrent and complicated respiratory tract infections. Before the 1980s, little was known about the clinical manifestation of immunodeficiency in the general medical population, and also the availability of serum immunoglobulin laboratory determination was not sufficient, leading to a significant diagnostic delay. METHODS: We have analysed the diagnostic delay and referral diagnoses in patients in whom any form of primary hypogammaglobulinaemia had been diagnosed at our department, which was established in 1981. RESULTS: Comparing the diagnostic delay in the 1980s (19 patients, median 5.5 years), the 1990s (37 patients, median 3.5 years) and the years 2001-2008 (33 patients, median 1 year), a significant decrease was observed (p < 0.05, Spearman's correlation coefficient). Also, the median number of pneumonia episodes during the diagnostic delay decreased from 5 in the 1980s, to 1 in the 1990s and to 0 in the period of 2001-2008 (p < 0.05, Spearman's correlation coefficient). While in the 1980s 17 of the 19 patients had pneumonia in their past history, in the period of 2001-2008 only 13 of the 33 patients were concerned. CONCLUSIONS: Our observation documents improved awareness of immunodeficiencies among physicians. It is supposed that earlier diagnosis will prevent complications, improve the quality of life and even survival of hypogammaglobulinaemic patients.

Postnatal functional maturation of blood phagocytes in pig.

Developmental changes of functional ability of peripheral blood phagocytes from days 1 to 100 of life were investigated. Luminol enhanced chemiluminiscence was used to establish the ability of phagocytes to produce reactive oxygen species (ROS). Simple superoxide anion production was determined by spectrophotometrical measurement of cytochrome c. Activity of surface aminopeptidase N was assessed by spectrophotometrical measurement of l-alanine-p-nitroanilide. Flow cytometric measurements of CD18 and CD45 expression were performed. The ROS production per 0.5microl of blood did not show any trend; however, the values recalculated per 500 granulocytes had a decreasing course. The most noteworthy increase in production of superoxide anion occurred between days 17 and 26. Activity of aminopeptidase N decreased during the first 4 weeks. Expression of CD18 and CD45 intensively increased from days 1 to 14 with gradual decrease by day 100. Natural immunity develops during the early postnatal life and seems to be influenced by exposure of the organism to environmental antigens.