Antinuclear antibodies positivity is not rare during multiple sclerosis and is associated with relapsing status and IgG oligoclonal bands positivity.

INTRODUCTION: As an immune-mediated disease of the central nervous system, multifaceted aspects of a humoral immune response are widely described during multiple sclerosis (MS). However, the prevalence of different auto-antibodies, such as antinuclear antibodies (ANA), during MS is very variable and their clinical relevance remains controversial. Our aim was to evaluate the prevalence and clinical correlations of ANA positivity in South Tunisian MS patients. MATERIAL AND METHODS: We performed ANA screening using indirect immunofluorescence (IIF) on HEp-2 cells (Biosystems®) in 82 MS patients. For ANA positive samples (titer ≥1/160), anti-ds-DNA detection (IIF on Crithidia luciliae (Biosystems®)) and extractable nuclear antigen typing (immunodot (Euroimmun®)) were performed. RESULTS: ANA were positive in 35/82 MS patients (42.7%). The titer was ≥1/320 in 16/35 patients. The antigenic specificity of ANA was identified in 7/35 patients. None of the patients had extra-neurological manifestations. No correlation was found between ANA and age, gender, MS course, disease duration, disability, annual relapse rate nor IgG index. ANA positivity was more frequent in patients with IgG oligoclonal bands (OCB) (47.1%) than in patients without IgG OCB (16,6%) (p=0.049). Regarding disease activity, ANA positivity was significantly more frequent in patients with relapse (52.6%) than in patients in remission (25.9%) (p=0.031). CONCLUSION: Our results showed that ANA positivity in MS disease is not rare. This positivity was not associated with clinical expression of any connective tissue disease. ANA occurrence in MS was associated with IgG OCB+ profile and relapsing status, probably reflecting an ongoing immune dysregulation.

[Variations in immunological parameters after treatment of a manic episode]. / Variations immunologiques après traitement d'un épisode maniaque.

Bipolar disorder is a chronic and disabling mental illness affecting approximately 1-2% of the general population, characterized by the occurrence of manic episodes alone or alternating with depressive episodes. Bipolar disorder is associated with significant morbidity, mortality and personal suffering. The mechanisms underlying the onset and progression of bipolar disease are still poorly understood. Recently, immunological dysfunctions have been suggested in the pathogenesis of bipolar disorder, and many studies have focused on the interaction between bipolar disorder and immunity. Immunological changes have been widely studied during depressive episodes but less explored during manic episodes. The objective of our study was to explore changes in serum proteins and autoantibodies after treatment for a manic episode of bipolar I disorder. This study was carried out over a 30-month period from January 2017 to June 2019, in collaboration between the psychiatry department B of the Hédi Chaker CHU and the immunology department of the Habib Bourguiba CHU, in Sfax, Tunisia. It focused on a sample of 45 bipolar patients with manic relapse, naïve to psychotropic treatment, or discontinuing treatment for a period of at least three months and without a history of autoimmune disease. The study was conducted in two stages : on admission and after treatment. The mean plasma levels of IgG and complement C3 fraction were significantly higher in bipolar patients with relapsing mania. Studies of variation in immunoglobulins and complement fractions during relapses of bipolar disorder have all objected to variations in these serum proteins, but their results were inconsistent regarding the direction of variation and the fractions affected. After treatment, there was a statistically significant increase in the mean plasma levels of IgG and IgA and a decrease in the mean plasma level of the C4 fraction of complement. No significant variation in autoantibodies was noted after treatment. The mean plasma IgM level was significantly lower with sodium valproate. On atypical antipsychotic medication, the mean plasma level of fraction C3 was statistically lower, whereas on conventional antipsychotic medication it was statistically higher. This is in line with the data in the literature which support the immunomodulatory role of thymoregulators and antipsychotics. Serum proteins have been more sensitive than autoantibodies to the effect of psychotropic therapy during manic relapse.

Neuromyelitis optica spectrum disorders in South of Tunisia: A rare entity with low seroprevalence of anti-aquaporin 4 autoantibodies.

INTRODUCTION: Screening for anti-aquaporin 4 (anti-AQP4) antibodies, a specific marker of neuromyelitis optica spectrum disorders (NMOSD), is part of the immunological investigation performed in a context of central nervous system (CNS) inflammation with optic neuritis and/or myelitis. The aim of our study was to evaluate the prevalence and the diagnostic value of anti-AQP4 antibodies in Tunisian patients with such inflammatory neurological conditions. METHODS: During 3years, 170 consecutive serum samples of Tunisian patients with CNS inflammatory disorders and optico-spinal involvement were tested in our laboratory for anti-AQP4 antibodies using indirect immunofluorescence on transfected cells. RESULTS: The global seroprevalence of anti-AQP4 in our study was 4.1% (7 cases/170). The diagnosis of NMOSD was made for the 7 seropositive patients and for 2 seronegative patients, which leads to a seroprevalence of 77.7% in our NMOSD subgroup. The detection of anti-AQP4 allowed the diagnosis of NMOSD in 4 patients with incomplete clinical presentation and 5 patients with positive antinuclear antibodies. In one case, seropositivity was detected in a second sample, one year after an initial seronegativity. CONCLUSION: NMOSD seem to represent a rare etiology of optic neuritis and/or myelitis in Tunisian patients. Despite its low global seroprevalence in our study population, anti-AQP4 appears to be a very clinically relevant marker for NMOSD diagnosis. Repeating the screening in case of initial negativity could be interesting in clinical practice.

Relevant genetic polymorphisms and kidney expression of Toll-like receptor (TLR)-5 and TLR-9 in lupus nephritis.

Toll-like receptor (TLR) genetic polymorphisms may modify their expression causing inflammatory disorders and influencing both susceptibility and severity of lupus erythematosus. We aim to determine whether TLR-5 and TLR-9 gene polymorphisms are implicated in the susceptibility to systemic lupus erythematosus (SLE) and lupus nephritis (LN) and to evaluate their expressions and distributions in renal LN patients' biopsies. The frequencies of two SNP in the TLR-9 gene and one in the TLR-5 gene was examined in 106 SLE patients (among them 37 LN patients) and in 200 matched controls by polymerase chain reaction-restriction fragment-length polymorphisms (PCR-RFLP) analysis. TLR-9 and TLR-5 expressions were assessed by reverse transcription (RT)-PCR and immunohistochemistry carried on LN renal biopsies compared to healthy renal tissue. A significant genotypic and allelic association was revealed between TLR-9-rs352140 and both SLE and LN (P < 0·05). The TLR-9 transcript level was significantly higher in LN biopsies compared to control (P < 0·05). This increase was observed histochemically in the tubulointerstitial compartment. TLR-9 was detectable in LN glomeruli patients but not in normal control glomeruli. No allelic nor genotype association was found with TLR-5-rs5744168 in SLE. but the T allele and the TT genotype were raised significantly in the LN group (P < 0·05). A significant increase in TLR-5 gene expression in LN biopsies, which contrasted with normal kidneys (P < 0·05), was confirmed by an intense and diffuse staining for TLR-5 only in LN tubules (P < 0·05). Our data show that TLR-5 and TLR-9 are susceptible genes to LN and that their expression is dysregulated in LN patients' kidneys, supporting a role of these mediators in the pathogenesis of LN.

Polymorphism of the N-acetyltransferase 2 gene as a susceptibility risk factor for antituberculosis drug-induced hepatotoxicity in Tunisian patients with tuberculosis.

SETTING: Antituberculosis drug-induced hepatitis attributed to isoniazide (INH) is one of the most prevalent drug-induced liver injuries. INH is metabolized by hepatic N-acetyltransferase 2 (NAT2) to form hepatotoxins. AIM: To evaluate whether polymorphism of the NAT2 gene was associated with antituberculosis drug-induced hepatotoxicity in Tunisian patients. METHODS: A total of 66 patients with tuberculosis (TB) who received anti-TB treatment were followed prospectively. Their NAT2 genotype was determined using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). We identified three single nucleotide polymorphisms (SNPs); 481C to T (NAT2*5B), 590G to A (NAT2*6A) and 857G to A (NAT2*7B). Univariate analysis and logistic regression analysis were used to evaluate the risk factors of isoniazid-induced hepatitis. RESULTS: Fourteen patients (21.2%) were diagnosed with anti-TB drug-induced hepatitis. None of the rapid acetylators-type patients have expressed serum aminotransferase elevation. Among patients with hepatotoxicity, slow acetylators-type patients had a higher risk of hepatotoxicity than intermediate acetylators (21.4% vs. 78.6%, P=0.01). Statistical analysis revealed that the frequency of a variant diplotypes, NAT2*5B/5B and NAT2*6A/6A, were significantly increased in TB patients with hepatotoxicity, compared with those without hepatotoxicity (P=0.01, odds ratio [OR]=7.6 and P=0.029, OR=15, respectively). By contrast, the frequency of the rapid acetylation NAT2*4 allele was significantly lower in TB patients with hepatotoxicity than those without hepatotoxicity (P=0.02, OR=0.18). Moreover, 590G/G genotype was associated with decreased hepatotoxicity (P=0.01); by contrast, homozygous point mutation at position 481 and 590 were associated with a higher risk of hepatotoxicity (P=0.01). CONCLUSION: Our results suggest that the slow-acetylator status of NAT2 is risk factor for INH-induced hepatotoxicity. Moreover, diplotypes, NAT2*5B/5B, NAT2*6A/6A, 481T/T and 590A/A, are useful new biomarkers for predicting anti-TB drug-induced hepatotoxicity.

Paranasal sinus osteomas: Diagnosis and treatment.

INTRODUCTION: Osteoma is the most common benign tumor of the nose and paranasal sinuses. It is a slow-growing bony tumor, often asymptomatic, occurring mainly in frontal and ethmoid sinuses. Theories regarding the origin of osteomas are still discussed. The aims of the study were to describe diagnosis circumstances in our series and to set out our respective indications for open and endoscopic approaches in the treatment of nasosinusal osteomas. PATIENTS AND METHODS: A retrospective study was conducted on the files of all the patients treated for a paranasal sinus osteoma in our department between 1990 and 2013. Diagnosis circumstances and kind of treatment were collected and analyzed. RESULTS: The files of 45 patients (mean age: 49.2; sex-ratio: 1.19) could be collected. The most common symptom was headache found in all patients. The most common location was the frontal sinus (30 cases). Thirty-nine open procedures were performed. Four osteomas were removed under endoscopic assistance. In one case, a combined approach has been used. Overall complication rate was 11.1%. Symptoms improved in all patients. Two recurrences were observed. DISCUSSION: Surgical indications in paranasal sinus osteomas are theorically well codified. However, approaches remain controversial. In our experience, the preferred approach was the open one. Endoscopic techniques, when indicated, are more challenging and need sophisticated instrumentation and a long learning curve.

[Neonatal lupus and maternofetal transmission of anti-SSA/Ro and anti-SSB/La antibodies]. / Lupus néonatal et transmission materno-fœtale des anticorps anti-SSA/Ro et anti-SSB/La.

Neonatal lupus (NL) is a rare syndrome caused by placental transfer of maternal anti-SSA/Ro (60 and 52kDa) or anti-SSB/La antibodies. The aim of this study was to evaluate the clinical and biological profile of NL at the neonatal unit of Sfax, Tunisia, over a 10-year period. Six mother-NB pairs (two sets of twins and two sisters) had positive ANA by transplacental transmission during the study period. The ANA pattern was speckled and the NBs' sera titer was half that of their mothers'. Anti-SSA, anti-Ro52, and anti-SSB were found in 100%, 33%, and 50% of the mothers' sera, respectively. The transmission of anti-SSA was observed in four pregnancies out of six, anti-Ro52 in two pregnancies out of two, and anti-SSB in one pregnancy out of three. The patients' clinical records showed that two NBs had a congenital heart block: one with anti-SSA, whose mother had Sjögren syndrome, and another with anti-SSA, anti-SSB, anti-Ro52, and anti-mitochondrial antibodies (M2 type), whose mother had no diagnosis at the child's birth (cutaneous erythema and positive ANA with the same profile). Cutaneous signs (erythema, petechia) were described in three NBs out of six. The two sets of fraternal twins had cutaneous signs with the same ANA titer and profile (no anti-SSA transmission from their mother with lupus and anti-phospholipid syndrome). The two sisters' (two pregnancies 3 years apart) mother had Sjögren syndrome, one of them had heart block with positive anti-SSA, and the other was asymptomatic with anti-SSA and anti-Ro52. The same mother had a history of three pregnancies with two NBs who died of heart block.