Anti-C1q antibodies and systemic lupus erythematosus in the Tunisian population.

OBJECTIVES: The presence of a wide variety of autoantibodies is a characteristic feature of systemic lupus erythematosus (SLE). Although non-specific, anti-complement C1q (anti-C1q) were shown to correlate with the occurrence of active nephritis. The present study aimed to investigate the prevalence of anti-C1q in Tunisian SLE patients and their association with clinical manifestations, especially renal involvement. PATIENTS AND METHODS: IgG anti-C1q antibodies were assessed by Elisa in 98 SLE patients, 55 patients with rheumatoid arthritis (RA) and 65 healthy individuals (HI). RESULTS: Anti-C1q were found in 53 (54.1%) patients with SLE, three (5%) patients with RA and six (9.3%) HI. Among the 65 patients with renal involvement, anti-C1q were present in 35 (53.8%) patients. There was no significant association between anti-C1q and renal or extrarenal manifestations. In addition, there was no correlation between anti-C1q titer and SLEDAI index. Anti-C1q were significantly associated with anti-nucleosome (P=0.001), anti-Sm (P=0.01) and a low C4 level (P=0.046). Concomitant presence of anti-C1q and anti-dsDNA antibodies was not associated with renal manifestations. CONCLUSION: Our study shows that prevalence of anti-C1q was comparable with that previously reported in Caucasian populations. These antibodies were associated with a low C4 level. However, there was no association between anti-C1q and renal involvement or severity of nephritis.

Prevalence of antineutrophil cytoplasmic antibodies during treatment with benzylthiouracil.

BACKGROUND: Drug induced antineutrophil cytoplasmic antibodies (ANCA) associated vasculitis is a rare complication associated especially with propylthiouracil (PTU). Prevalence of ANCA in patients receiving PTU is well established. Few cases of vasculitis were also reported with benzylthiouracil (BTU). The objective of this study is to clarify the prevalence of ANCA in patients receiving BTU. METHODS: ANCA were investigated by indirect immunofluoresence and enzyme linked immunosorbant assay in 159 patients with Graves' disease (86 untreated and 73 treated with BTU). RESULTS: ANCA were positive in three (3.5%) untreated patients and 27 (37%) treated ones. Titres of ANCA varied between 1:20 and 1:200. There was a significant association between BTU treatment and ANCA (p<0.001). ANCA were directed against myeloperoxidase (MPO) in 28 (93.3%) patients. Median treatment duration was 24 months (ranges 0.5 to 144 months). There was no significant association between treatment duration and ANCA. Vasculitis was found in two (2.7%) treated patients. One patient has developed isolated cutaneous vasculitis and the other one a pulmonary vasculitis with diffuse alveolar haemorrhage. CONCLUSION: BTU therapy is characterised by a high prevalence of ANCA mainly but not exclusively directed against MPO. However, vasculitis remains a rare complication.

[Antineutrophil cytoplasmic antibodies and associated diseases]. / Anticorps anticytoplasme des polynucléaires neutrophiles et pathologies associées.

Antineutrophil cytoplasmic antibodies are classical serological markers of small-vessels vasculitis. However, they have been described in many other pathological situations. The aim of this study was to determine through our experience, the main antineutrophil cytoplasmic antibodies-associated diseases and to investigate antigen targets of these antibodies. Forty complete observations of antineutrophil cytoplasmic antibodies (ANCA) positive patients either by indirect immunofluorescence or by enzyme immunoassay were analysed. Only five (12.5%) patients have small-vessels vasculitis. Among these, antineutrophil cytoplasmic antibodies were detected only by Elisa in one patient and they were exclusively directed against bactericidal permeability increasing protein in another one. Our study confirms the presence of antineutrophil cytoplasmic antibodies in different diseases. It demonstrates that antineutrophil cytoplasmic antibodies should be investigated by Elisa when indirect immunofluorescence is negative. In small-vessels vasculitis, Proteinase 3 and myeloperoxidase are mainly but not exclusively the antigenic targets of antineutrophil cytoplasmic antibodies.

Gamma interferon is dispensable for neopterin production in vivo.

Previous studies have indicated that neopterin is synthesized in vitro by human monocyte-derived macrophages and dendritic cells upon stimulation with gamma interferon (IFN-gamma). Neopterin production under specific conditions in vitro has also been obtained upon stimulation with IFN-alpha and/or IFN-beta. However, it is unknown if any IFN-gamma-independent neopterin synthesis is possible in vivo. In the present study we investigated the serum neopterin concentrations in patients affected by the syndrome of Mendelian susceptibility to mycobacterial disease (MSMD). Indeed, this syndrome is characterized by deeply impaired or absent IFN-gamma production or function due to severe mutations in molecules involved in IFN-gamma/interleukin-12 (IL-12)/IL-23-dependent pathway. Serum neopterin levels were measured by an enzyme-linked immunosorbent assay in 27 patients with MSMD. We found that serum neopterin levels are elevated in the complete absence of IFN-gamma activity due either to a complete deficiency of its receptor or to deleterious mutations of IL-12 or its receptor. These data clearly indicate that, as reported from in vitro studies, other stimuli are able to induce neopterin synthesis in vivo. Consequently, neopterin cannot be used as means of diagnosis of MSMD due to IFN-gamma-, IL-12-, and IL-23-dependent pathway defects.

[Analytic study of dot blotting for the detection of anti-Jo-1, anti-M2, anti-ribosomes and anti-LKM]. / Etude analytique d'un dot blot pour la détection des auto-anticorps anti-Jo-1, anti-M2, anti-ribosomes et anti-LKM1.

The Cyto-Dot 4 HM043 kit commercialised by BMD, has replaced the Cyto-Dot HM010 kit that allowed three auto-antibodies detection (anti-Jo-1, anti-M2 and anti-ribosomal protein). Detection of anti-LKM1 auto-antibody was added. These four auto-antibodies have in common only the intracytoplasmic localisation of their respective antigen. The aim of our study was to evaluate this new kit using 104 sera and to compare our results with reference techniques (indirect immunofluorescence IF for anti-M2, anti-ribosomal protein and anti-LKM1, double immunodiffusion ID for anti-Jo-1 and anti-LKM1, western blotting WB for anti-M2) and with Cyto-Dot HM010. The one hundred and four sera were divided into five groups: Group I (n = 12) with anti-Jo-1 detected by ID; Group II (n = 28) with 26 anti-M2 positive by IF and WB, 2 anti-M2 positive only by WB; Group III (n = 10) with anti-ribosomal protein detected by IF 5 of which precipitated by ID; Group IV (n = 32) with anti-LKM1 by IF and ID divided into 18 AIH2 and 14 HCV; Group V (n = 22) consisting of 14 healthy individuals and 8 patients with hypergammaglobulinemia. Results of this study are similar to those of Cyto-Dot HM010 for the three auto-antibodies already in use. Cyto-Dot 4 is a very good anti-LKM1 confirmation method as it is ID.

DPB1 disparities contribute to severe GVHD and reduced patient survival after unrelated donor bone marrow transplantation.

In order to evaluate the impact of HLA-DBP1 incompatibilities on the occurrence of acute graft-versus-host disease (GVHD) in unrelated hematopoietic cell transplantation, we studied 57 donor/recipient pairs characterized by their allelic identity for HLA-A, B, C, DRB1 and DQB1 and also for DRB3, 4, 5 loci and aimed to correlate DPB1 mismatches to already described risk factors for GVHD using multivariate Cox regression analysis. DPB1 identity between donor and recipient was observed in 24% and DPB1 compatibility (GVHD vector) in 42%. Two factors were independently associated with severe acute GVHD: two DP incompatibilities (RR = 8.25, 95% confidence interval (CI): 1.67-40.10, P = 0.010) and disease risk (RR = 10.23, 95% CI: 1.12-93.13, P = 0.012). Two DPB1 incompatibilities appeared also to be a factor in poorer survival independent of its effect on acute GVHD (RR = 4.97, 95% Cl: 1.80-13.71, P = 0.002). A correlation between acute GVHD and matching for each individual DPB1 polymorphic region and for residue 69 of the DP beta molecule, which seems to be a key residue in the alloimmune response, was not observed. Our data indicate that the outcome of unrelated hematopoietic cell transplantation in terms of GVHD but also survival, could be improved through HLA-DPB1 matching or at least by avoiding two DPB1 mismatches.

Two novel CD1 E alleles identified in black African individuals.

CD1 gene (CD1A to CD1E) products are involved in non-peptide antigen presentation, such as lipids and glycolipids, to T cells. With a similar function to MHC, namely antigen presentation, these genes nevertheless displayed a much lower level of polymorphism as compared to MHC. We report here two additional CD1E variants identified in black African individuals, designated herein CD1E*05 and CD1E*06. While the former differs from the common (wild type) allele sequence by two substitutions at nucleotide positions 217 and 229 of exon 2, the latter only by a single base change at position 91 of exon 3. These substitutions lead to amino acid changes at position 73 and 77 of the alpha1 domain in the former and at position 30 of the alpha2 domain in the latter. Identification of these additional variants suggests that the CD1 locus, especially the CD1E gene, is much more polymorphic than previously assumed.

A new HLA-Cw allele (Cw*1510), identified in a French Caucasian individual.

A novel HLA-Cw*15 allele, Cw*1510, found in a French Caucasian bone marrow recipient is described. Nucleotide sequence of the new variant is identical to the common Cw*15021 DNA sequences except nucleotides at positions 32 and 61 of exon 2. While the first difference is silent, the second cause substitution of an Histidine by an Arginine at amino acid position 21 of the alpha1 heavy chain domain.

[Anti-endomysium, anti-reticulin and anti-gliadin antibodies, value in the diagnosis of celiac disease in the child]. / Anticorps anti-endomysium, anti-réticuline et anti-gliadine, intérêt dans le diagnostic de la maladie coeliaque chez l'enfant.

Coeliac disease is associated with gluten intolerance in genetically predisposed subjects. Environmental factors, particularly of viral origin, may also play a major role. In this study, the presence of IgA class anti-endomysium antibodies (AEA-IgA), IgA class anti-reticulin antibodies (ARA-IgA) and IgA class anti-gliadin antibodies (AGA-IgA) was investigated in 120 serum samples from 120 children (60 patients with coeliac disease and 60 control subjects). The AEA were detected by indirect immunofluorescence on sections of human umbilical cord. The ARA were also investigated by the same technique in rat kidney, liver and stomach. The AGA were determined by an enzyme-linked immunosorbent assay (ELISA). In the patients with coeliac disease, the sensitivity of AEA and ARA was 86% and 76% respectively. In both cases, the specificity was 100%. In children below two years of age, the sensitivity of AEA and ARA was too low, i.e., 57% and 35% respectively. In children aged between two and 15 years, the sensitivity of AEA and ARA was 95% and 89% respectively. The sensitivity of IgA class AGA was 86%, and their specificity was 83%. In this study population, these results show that IgA class AEA are interesting markers for the diagnosis of coeliac disease in the child, and could be used in screening for coeliac disease in a high-risk population.

[Chronic septic granulomatous disease. 14 cases]. / Granulomatose septique chronique. 14 observations.

OBJECTIVES: Chronic granulomatous disease (CGD) is a rare inherited immunodeficiency. Affected children are mostly boys. The most common clinical features are recurrent bacterial and fungal infections starting at early childhood. We report 14 cases, including 5 girls, of CGD in Tunisian children. PATIENTS AND METHODS: This retrospective study concerned 14 clinical observations of CGD recorded between April 1988 and December 1998. The diagnosis was established upon determination of a defective respiratory burst in the patients' neutrophils at the tetrazolium nitroblue test (NBT). In 4 cases, the diagnosis was also confirmed by chemiluminescence assay. RESULTS: The patients (9 boys and 5 girls) belonged to 12 families, 75% of which were consanguineous. In 6 families, there had been several deaths in early childhood. The mean age at onset of clinical signs was 6.8 months (7 days to 24 months). Clinical signs included lung (10 cases), nodal (8 cases), skin (7 cases), and intestinal (7 cases) infections. Seven patients developed invasive pulmonary aspergillosis with parietal extension in 4 cases. Salmonella and Staphylococcus infections were rare in our series. Six children (42.8%) including 2 girls, died. Aspergillosis was fatal in 4 cases. CONCLUSION: Recurrent infections are the main clinical fetus of chronic granulomatous disease. Prognosis has been improved by the use of prophylactic antibiotics. Early diagnosis of the disease is crucial.