Seventy-nine unrelated Lebanese patients were tested for 15 mutations in the MEFV gene: A761H, A744S, V726A, K695R, M694V, M694I, M694del, M6801 (G ® C), M680I (G ® A) in exon 10, F479L in exon 5, P369S in exon 3, T267I, E167D and E148Q in exon 2, using PCR digestion, ARMS, DGGE and/or sequencing. Mutations were detected in patients belonging to all communities, most interestingly the Maronite, Greek orthodox, Greek catholic, Syriac and Chiite communities. The most frequent mutations are M694V and V726A (27% and 20% of the total alleles respectively). M694I, E148Q and M680I mutations account respectively for 9%, 8% and 5%. Each of the K695R, E167D and F479L mutations was observed once and all the remaining mutations were not encountered. Of the alleles 33% do not carry any of the studied mutations. The mutation spectra, clinical features and severity of the disease differed among the Lebanese communities. The genotype-phenotype analysis showed a significant association (P < 0.001) between amyloidosis and the presence of mutations at codon 694 in exon 10 (both M694V and M694I). None of the patients carrying other mutations developed amyloidosis. European Journal of Human Genetics (2001) 9, 51-55.

IgD is a minor component of serum Ig and the control of IgD secretion is virtually unknown. We measured concentrations of IgD (and IgE and IgM as controls) in culture supernatants of peripheral blood mononuclear cells (PBMC) from 60 normal donors as well as mononuclear cells from 10 tonsils following culture in the absence or presence of CD40 mAb and cytokines. Low levels of IgD were measured in cultures of PBMC, either unstimulated or stimulated by anti-CD40 antibodies. IL-4 and IL-10 significantly increased IgD production by CD40 mAb-stimulated cells in the majority of normal subjects studied, whereas in a limited number of individuals, spontaneous IgD production was either low or high, but with no increase upon stimulation. Spontaneous IgD production by tonsil-derived mononuclear cells was higher than by PBMC and increased after CD40 stimulation and even more in the presence of IL-10, but not IL-4. IL-2 and IFN-gamma exerted a dose-dependent inhibition on spontaneous as well as CD40- and cytokine-induced IgD production by PBMC, but not by tonsil mononuclear cells. Activation by IL-4 of CD40-stimulated purified B cells from tonsil and PBMC, and by IL-10 of tonsil B cells increased IgD production, whereas IL-2 and IFN-gamma had no detectable inhibitory effect. This suggests that accessory cells indirectly regulate IgD synthesis. IgD production induced in PBMC by IL-4 or IL-10 appeared to result from an active synthesis, and correlated with an increase in the number of IgD-containing plasma cells as demonstrated by immunofluorescence and increased expression of secreted IgD transcripts. These findings suggest that IgD production by normal peripheral blood human B cells is regulated positively by T(h)2 cytokines and negatively by T(h)1 cytokines.

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