High prevalence of antineuronal antibodies in Tunisian psychiatric inpatients.

The authors aimed to determine the prevalence of antineuronal antibodies in 103 psychiatric inpatients and 41 control subjects with no history of malignancies or neurological disorders. All sera were tested by indirect immunofluorescence and positive sera by immunoblot. Using immunofluorescence, antineuronal nuclear autoantibodies were detected in 20 patients and none of the control subjects, and antibodies reacted with the cytoplasm of Purkinje cells in six patients and two control subjects. The immunoblot confirmed well-characterized antineuronal antibodies only in five patients: two had anti-Ri and three had anti-Yo antibodies. After a follow-up of 5 years, none of these patients developed neurological disorder or malignancy.

Spectrum of autoantibodies in Tunisian psychiatric inpatients.

One hundred and three psychiatric inpatients (74 men) were assessed for a wide spectrum of autoantibodies including antinuclear, antismooth muscle, antimitochondrial, antiDNA, anti-phospholipid, anti-cardiolipin IgG and IgM, antikeratin, rheumatoid factor, antithyroperoxydase, antigliadin IgA and IgG, antitransgutaminase, and antiendomysium antibodies. Four groups of patients were considered separately, including 47 with schizophrenia, 23 with schizoaffective disorder, 16 with bipolar disorder and 17 patients with other different psychiatric diagnosis. Forty one healthy, age- and sex-matched blood donors were used as a control group. There were no significant difference in the prevalence of the different autoantibodies between patients (N = 103) and controls except for antigliadin IgG (30.1 vs 9.8 respectively, p = 0.01). Presence of autoantibodies was influenced by age but not by sex or treatment. As for diagnosis categories, patients with bipolar disorder presented significantly more autoantibodies than the three other categories and controls. These results point out a possible autoimmune activation in at least a subgroup of psychiatric patients especially amongst those suffering from bipolar disorder.

HLA class II alleles susceptibility markers of type 1 diabetes fail to specify phenotypes of ketosis-prone diabetes in adult Tunisian patients.

We aimed to characterize the different subgroups of ketosis-prone diabetes (KPD) in a sample of Tunisian patients using the Aß scheme based on the presence or absence of ß-cell autoantibodies (A+ or A-) and ß-cell functional reserve (ß+ or ß-) and we investigated whether HLA class II alleles could contribute to distinct KPD phenotypes. We enrolled 43 adult patients with a first episode of ketosis. For all patients we evaluated clinical parameters, ß-cell autoimmunity, ß-cell function and HLA class II alleles. Frequency distribution of the 4 subgroups was 23.3% A+ß-, 23.3% A-ß-, 11.6% A+ß+ and 41.9% A-ß+. Patients from the group A+ß- were significantly younger than those from the group A-ß- (P = .002). HLA susceptibility markers were significantly more frequent in patients with autoantibodies (P = .003). These patients also had resistance alleles but they were more frequent in A+ß+ than A+ß- patients (P = .04). Insulin requirement was not associated to the presence or the absence of HLA susceptibility markers. HLA class II alleles associated with susceptibility to autoimmune diabetes have not allowed us to further define Tunisian KPD groups. However, high prevalence of HLA resistance alleles in our patients may reflect a particular genetic background of Tunisian KPD population.

Is the rapid whole blood test useful for diagnosis and monitoring celiac disease in children?

AIM: To evaluate a new whole blood rapid test for the detection of IgA anti-transglutaminase (ATG) for diagnosis and diet survey of celiac disease (CD). METHODS: 57 children, 20 of them were CD patients on a gluten-free diet and 37 were under suspicion of CD were enrolled. IgAATG was detected by the conventional ELISA test and the new rapid whole blood test. RESULTS: Concordance between the 2 tests was 96.4%. All patients positive with ELISA were also positive by the rapid test. Only 2 patients were slightly positive by the rapid test and negative by ELISA. CONCLUSION: Whole blood rapid test seems to be as performant as ELISA test for IgAATG detection.

HLA-B, DR and DQ antigens polymorphism in Tunisian patients with ankylosing spondylitis (a case-control study).

The objective of the study is to assess the distribution of HLA-B genes, HLA-B27 subtypes, HLA-DRB1 and HLA-DQB1 alleles in patients with ankylosing spondylitis (AS) and in control subjects in the Tunisian population and to compare their distribution with that found in other countries. This is a case-control study that included 100 consecutive patients (85 males/15 females) with AS according to the modified New York criteria and 100 control individuals. HLA-B, B27 subtypes and class II (DR and DQ) typing of all subjects was performed by polymerase chain reaction amplification with sequence-specific primers (PCR-SSP). HLA-B27 was found in 62% of patients against 3% in controls (P = 0.0000, OR = 52.6, 15.6 < CI < 166.7). On the other hand, B*07 and B*51 were significantly decreased in comparison with controls (P = 0.01, OR = 0.3, 0.1 < CI < 0.8 and P = 0.0000, OR = 0.2, 0.1 < CI < 0.4, respectively). Eight B*27 subtypes were identified in the AS group, but the most frequent ones were B*2702 (32%) and B*2705 (24%). Among HLA-DRB1 alleles, a significant increase in DRB1*11 was found in comparison with controls (P = 0.01, OR = 2.2, 1.2 < CI < 4.5). However, DRB1*13 had a negative association with AS (P = 0.01, OR = 0.4, 0.2 < CI < 0.8). For HLA-DQB1 alleles, a significant positive association with DQB1*03 was observed in AS group (P = 0.03, OR = 1.8, 1.0 < CI < 3.4). Multivariate analysis by logistic regression revealed that DRB1*11 and DQB1*03 had no direct links with the disease, but were dependent on the presence of HLA-B27. Moreover, B*07 and B*51 seemed to have independently a negative correlation with AS, but DRB1*13 seemed to depend on B*51. Haplotypes carrying B27 were significantly associated with AS and those carrying B*07 or B*51 were negatively correlated with the disease. In conclusion, our study confirms that B27 predisposes to AS while B*07 and B*51 are negatively correlated with the disease.

HLA class II polymorphism in children with coeliac disease in Tunisia: is there any influence on clinical manifestation?

OBJECTIVE: To elucidate the HLA DRB1, DQB1 and DQA1 polymorphism in Tunisian children with typical form of coeliac disease (CD) in comparison with those from mass screening (atypical and silent CD). MATERIALS AND METHODS: We recruited three groups: group I: 40 CD children diagnosed according to the ESPGHAN criteria. group II: 40 healthy controls matched with sex, age and geographic origin. group III: 38 CD children coming from mass screening in schoolchildren. HLA class II DRB1, DQB1 and DQA1 alleles were typed by PCR-sequence-specific primer. RESULTS: Comparing the groups I and II, we found a pronounced increase of the susceptible alleles HLA DRB1*03 (relative risk, RR = 4.18, Pc = 0.001), DQB1*02 (RR = 7.9, Pc<0.0001) and DQA1*0501 (RR = 4.1, Pc = 0.001). As for protective alleles, we detected a high frequency of DRB1*13 (RR = 0.059, Pc = 0.001), DQA1*0102 (RR = 0.071, Pc = 0.009) and DQB1*06 (RR = 0.125, Pc = 0.0042). Haplotype analysis showed that the main combination observed was the conformation of DQ2 (DQA1*0501-DQB1*02) in 36 patients from group I and 30 from group III. There was no statistically significant difference between the groups I and III according to the distribution of the different alleles. CONCLUSION: We confirmed in this study the high frequency of DQ2 haplotype in CD patients and we identified new protective alleles DRB1*13, DQA1*0102 and DQB1*06. However, HLA polymorphism seems to have no evident impact on clinical outcome of CD.

Spectrum of autoantibodies in Tunisian adult type 1 diabetes mellitus.

As an autoimmune disease, type 1 diabetes mellitus (T1DM) is characterized by the presence of several autoantibodies. The aim of this study was to examine a broad spectrum of antibodies in Tunisian adult T1DM and to compare their prevalence with a healthy control group. Two hundred sixty-one diabetics and 100 healthy blood donors were enrolled in this study. Indirect immunofluorescence was performed for the detection of islet cell, antiendomysial, antinuclear, antimitochondrial, antismooth muscle, antireticulin, and antikeratin antibodies. Enzyme-linked immunosorbent assay was used for measuring anticardiolipin, antigliadin, antitransglutaminase, and antithyroperoxidase antibodies. Latex agglutination was used for the detection of rheumatoid factors. As expected, islet cell antibodies were the most frequent (33.7%). Antigliadin, antithyroperoxidase, and antikeratin antibodies were relatively frequent (18%, 15.3%, and 10.3%, respectively) and were statistically more prevalent in diabetics than in controls. There was no correlation between diabetes duration and any autoantibody, except for islet cell antibodies that were more frequent at the onset of diabetes. Several autoantibodies nonspecific of diabetes are frequent in diabetic patients, which may be associated with or predictors of some autoimmune diseases, and can also reflect a special profile of autoimmunity in diabetics in comparison to healthy controls.

Hereditary complement deficiency and lupus: report of four Tunisian cases.

The aim of the study was to assess the clinical and immunological profile of lupus erythematosus (LE) patients with inherited complement deficiency (ICD). A laboratory-based study was conducted in which all LE patients with hypocomplementemia were included. ICD was assessed by hemolytic and antigenic assays. Type I C2 deficiency was assessed by polymerase chain reaction (PCR). ICD was diagnosed in four cases. In three systemic LE patients, ICD were: homozygous C2 deficiency in the first case, heterozygous C2 deficiency in the second, and homozygous C1q deficiency in the third case. In a discoid LE patient, a combined homozygous C2 and C6 deficiency was diagnosed. Almost all of our patients presented the classical clinical and immunological features of LE associated with ICD. Severe lupus with renal involvement and recurrent infections was present in half of the patients suggesting that these patients are prone to a serious management.

Pediatric systemic lupus erythematosus with C1q deficiency.

Hereditary deficiency of each component of the classical pathway is associated with increased susceptibility to lupus erythematosus (LE). Both the severity of the disease and the strength of this association are greatest for homozygous C1q deficiency, which is extremely rare. In fact, more than 90% of all individuals with deficiency of this component have LE. We report a 3-year-old female infant with history of discoid LE treated with topical corticosteroids for 1 year. She was referred to pediatric department for an exacerbation and extension of cutaneous lesions toward front-arm, hands, legs and feet, a glomerulonephritis, and thrombopenia. Immunologic tests revealed a positive speckled antinuclear antibody at 1/1600 with positive anti-Sm, anti-SSA, and anti-RNP antibodies. Test for anti-DNA was negative. These findings were compatible with a transition to a systemic form of lupus. Systemic corticosteroid treatment was started; however, the patient died by a severe digestive hemorrhage. Hemolytic complement activity (CH50) was undetectable in serum despite normal levels of C3 and C4 suggesting a deficiency of an early component of the complement cascade. Measurement of hemolytic assay for C1 functional activity was less than 1%. C1q deficiency was confirmed by a double immunodiffusion and ELISA using sheep polyclonal anti-C1q antibodies. C1q deficiency is a rare genetic disorder. Thirty-eight of the 41 patients reported to date have developed systemic LE. C1q deficiency may cause systemic LE via a critical role of this component in the physiological clearance of apoptotic cells.

Prevalence of anticardiolipin and anti-beta2-glycoprotein I antibodies in celiac disease.

The aim of this study was to evaluate the prevalence of anticardiolipin antibodies (aCL) and anti-beta(2)-glycoprotein I antibodies (abeta2GPI) in patients with celiac disease and to analyze the clinical features of antiphospholipid syndrome in these patients. We conducted a prospective case-control study based on the evaluation of IgG, IgM and IgA aCL, and IgG and IgA abeta2GPI in celiac disease patients and in controls. All patients were asked about any occurrence of thrombotic manifestations. In addition, women were asked about pregnancy morbidity. Fifty celiac disease patients and 50 healthy controls were studied. IgM aCL were not detected in study group or in controls. IgG aCL were found in two patients and in one control. IgA aCL were significantly more frequent in celiac disease patients compared with controls (13/50 (26%) vs. 2/50 (4%), p=0.004, OR [95% CI]=9.09 [1.81-50]). There was no statistically significant difference for the prevalence of IgG and IgA abeta2GPI between patients and controls. Clinical features of antiphospholipid syndrome were noted in two patients with negative antibodies. Prevalence of IgM and IgG aCL and of abeta2GPI were not increased in celiac disease. IgA aCL were more frequently detected in celiac disease. However, no clinical features of antiphospholipid syndrome were noted.

[Interest of serologic markers in inflammatory bowel disease. About 105 cases]. / Interet du dosage des marqueurs serologiques au cours des maladies inflammatoires cryptogenetiques de l'intestin. A propos d'une serie de 105 malades.

BACKGROUND: The serum markers ASCA and pANCA can help the clinician in certain difficult situations of colites in IBD. The aim of this study was to determine the sensitivity and the specificity of each one of these markers and to establish the characteristics of the positive patients for each one. METHODS: We included patients having a Crohn's disease (CD) or an ulcerative colitis (UC). These patients was compared to a control group. RESULTS: 80 CD patients with an average age of 35.62 years, 25 UC cases with an average age of 34.92 years and 79 healthy subjects with an average age of 34.2 years were included. The ASCA were detected in 33.8% of CD cases , 8% of UC cases of RCH and 2.5% of contro group (p < 000.1). The pANCA were detected in 48% of UC cases, 27.5% of CD patients and 1.3% of controls (p < 000.1). The sensitivity and the specificity of the ASCA and the pANCA for the diagnosis respectively of CD and UC were 33.8%, 97.5% and of 48%, 97.8%. During the CD, the positivity of the ASCA was significantly associated with ileal location (p = 0.001), with the sténosant and/or fistulisant phenotyp of the disease (p = 0.006), the young age at the time of the diagnosis of the CD (p = 0.067) and at a greater frequency of surgical treatment (p = 00.7). The pANCA were more frequently found in colic location of CD (p = 0.09). During UC, the positivity of the pANCA was not associated with the sex, age, loca tion of the disease, medical treatment nor chiurgical treatment. CONCLUSION: The ASCA and pANCA are useful during some clinical situations such as differentiation between IBD otherss colitis and to distinguish CD from UC.

Genetic factors in pemphigus.

Epidemiological studies performed in different ethnic populations and family studies, notably based on a partial phenotype of the autoimmune process, indicate that genetic factors are involved in the occurrence of pemphigus. However, the precise heritability remains uncertain in the absence of twin concordance rate studies. Among the different strategies available to identify genetic factors participating in autoimmune disease susceptibility, only population studies based on case-control design have been performed in pemphigus. These studies consistently showed that MHC locus, in particular HLA class II alleles, are associated with pemphigus vulgaris and pemphigus foliaceus. Other genes of the MHC locus may also participate in disease susceptibility as shown by studies using microsatellite markers across different regions of the MHC. It is likely that other non-MHC genes are involved in the pathogenesis of pemphigus. In particular, involvement of a polymorphic variant of desmoglein 1 gene was shown to be associated with pemphigus foliaceus and to interact in an epistatic manner with MHC class II genes to contribute to the autoimmune process. Other candidate genes to which a role can be assigned in the disease pathogenesis should be considered to design case-control or family-based association studies. Genome scan studies which require a large number of multiplex families to reach statistical power, should also be considered in the endemic form of pemphigus foliaceus because of the high number of familial cases.

Systemic lupus erythematosus with celiac disease: a report of five cases.

Systemic lupus erythematosus and celiac disease (CD) are rarely reported in combination. We report five cases seen over a 4-year period. The two conditions occurred concomitantly in one patient, whereas the CD antedated the lupus in one patient and postdated the lupus in the remaining three patients. Villous atrophy on duodenal biopsy specimens with a favorable response to a gluten-free diet was noted in all five patients. Only four patients had positive serological tests for CD and only three had abdominal symptoms.

[Recurrent pregnancy loss related to immune disorders]. / Pertes foetales et avortements spontanés à répétition d'origine immunologique.

Progress in immunologic methods and diagnostic assays over the last two decades has led the description of an association between some cases of recurrent fetal loss and recurrent spontaneous abortion of unknown cause to immunological factors. Some causal immunological diseases or dysregulations have been identified in pregnant women. These abnormalities may precede or be triggered by the pregnancy, or occasionally result from an impairment of the mother's allogeneic response to the fetus. In this article we review the principal immunological factors and abnormalities implicated in recurrent pregnancy loss and focusing on those generally accepted by the majority of authors.