Schizophrenia (SZ) and bipolar disorders (BD) are severe mental illnesses that lack reliable biomarkers to guide diagnosis and management. As immune dysregulation is associated with these disorders, ...we utilized the immunoregulatory functions of the natural killer cell inhibitory HLA-E locus to investigate the relationships between HLA-E genetic and expression diversities with SZ and BD risk and severity. Four hundred and forty-four patients meeting DSM-IV criteria for SZ (N = 161) or BD (N = 283) were compared to 160 heathy controls (HC). Circulating levels of the soluble isoform of HLA-E molecules (sHLA-E) were measured and HLA-E*01:01 and HLA-E*01:03 variants genotyped in the whole sample. sHLA-E circulating levels were significantly higher in both SZ and in BD patients compared to HC (pc < 0.0001 and pc = 0.0007 for SZ and BD, respectively). High sHLA-E levels were also observed in stable SZ patients and in acute BD patients experiencing depressive episodes when comparisons were made between the acute and stable subgroups of each disorder. sHLA-E levels linearly increased along HLA-E genotypes (p = 0.0036). In conclusion, HLA-E variants and level may have utility as diagnostic biomarkers of SZ and BD. The possible roles of HLA diversity in SZ and BD etiology and pathophysiology are discussed.
•BD are underpinned by dysimmunity and oxidative stress/ cellular senescence.•Mitchondria are at the cross road between stress, senescence and inflammation.•Low levels of mitochondria DNAcnv, a ...marker of mt dysfunction, are observed during manic episodes of BD and were correlated with disease severity and inflammation.•Peripheral inflammation was mainly reflected by high levels of adhesion molecules known to be involved in the brain barrier integrity.•Mitochondrial dyfunction may explain, at least partly, the inflammatory background often observed in bipolar disorders.
Mitochondria (Mt) are intra-cellular components essential for cellular energy processes whose dysfunction may induce premature cellular senescence and/or inflammation, both observed in bipolar disorders (BD). We investigated mitochondrial DNA copy number (mtDNAcn) levels in patients with BD being in manic, depressive or euthymic phase and in healthy controls (HC) both characterized for the levels of blood-based inflammatory markers and stigma of pathogens.
312 patients with BD were compared to 180 HC. mtDNAcn were measured using a digital droplet PCR. Serum levels of 14 inflammatory molecules and 3 anti-infectious IgG stigma were respectively evaluated by electro-chemiluminescence, ELISA and dedicated immunoassays. The statistical analyses were performed using Spearman’s correlation, Wilcoxon signed-rank and Kruskal-Wallis rank sum tests. P-values were adjusted for multiple testing with Benjamini-Hochberg method.
We found low levels of mtDNAcn in BD patients as compared to HC (P = 0.008) especially during manic episodes (P = 0.0002). We also observed that low levels of mtDNAcn are negatively correlated with mood and psychotic scales (PANSS, YMRS and CGI) (adjusted P (Adj P) = 0.02, 0.003 and 0.05 respectively) and positively with the GAF severity scale (Adj P = 0.002). They were also correlated with high levels of both intercellular adhesion molecule (ICAM)-1 and vascular cell adhesion molecule (VCAM)-1 (Adj P = 0.003 and 0.001) along with a trend toward increased IL-2, IL-10 and B2M circulating levels (Adj P = 0.05).
Here, we report correlations between marker of mitochondria functioning and both clinical scales and inflammatory markers in BD patients experiencing manic episodes. If replicated, these finding might allow to predict transition between disease phases and to design accurate therapeutic options.
Abstract Objective Monocyte Chemoattractant Protein-1 (MCP-1/CCL2), a key player in immune-mediated responses against Mycobacterium tuberculosis , is encoded by a polymorphic gene. Functionally ...relevant polymorphic variations in the MCP-1 gene have been associated with both susceptibility to and protection against tuberculosis-related disorders. Here, we investigated the potential impact of some of these polymorphisms on Pott’s disease risk in a patient cohort from Algeria. Methods DNA from 132 Algerian patients with exclusive Pott’s disease and 204 healthy controls, included under a case-control design, were analyzed for the MCP1 -2518A/G ( rs 1024611), -362G/C ( rs 2857656) and int1del554-567 ( rs 3917887) polymorphisms. PHASE software was used for haplotype reconstruction. Genetic associations were examined using chi-square tests. Results We found that the rs 1024611 -2518 GG, rs 2857656 -362 CC and rs 3917887 int1del554-567 del/del homozygous genotypes each were significantly more prevalent in patients than in controls (respective corrected p value Pc = 0.01, 0.04 and 0.04) Haplotype distribution profile further confirmed this, as the homozygous combination of GC del haplotype was also found with raised susceptibility to Pott’s disease ( Pc = 0.03). Conclusion Our findings confirm and replicate the recent data from China (which dealt essentially with rs 1024611 and rs 2857656) and also reinforce them by providing trans -ethnic evidence and extending the genetic association to the rs 3917887.
Toll-like receptors (TLRs) 2, 4, and the vitamin D receptor (VDR) are central components of the innate and adaptive immunity against Mycobacterium tuberculosis (Mtb). TLR2, TLR4, and VDR ...polymorphisms were previously associated with tuberculosis (TB) and were here investigated as candidates for pulmonary TB (PTB) susceptibility in a Moroccan population group.
Genomic DNA from 343 PTB patients and 203 healthy controls were analyzed for 12 single nucleotide polymorphisms (SNPs) located in TLR2, TLR4, and VDR genes using polymerase chain reaction-based restriction fragment length polymorphism and TaqMan SNP genotyping assays.
The TLR2 +597 CT genotype was associated with protection against PTB (corrected p pc = 0.04; odds ratio (OR) = 0.65; 95% confidence interval (CI) = 0.45 - 0.94), and the TLR4 +7263 C allele was significantly associated with PTB susceptibility (pc = 0.04; OR = 1.63; CI = 1.06 - 2.57). The VDR f,b,a,T haplotype was found to confer protection (pc < 0.00001; OR = 0.18; CI = 0.09 - 0.35), while the TLR2 -16934T,+597C,+1349T haplotype seemed to be at risk (p = 0.03; OR = 1.52; CI = 1.01 - 2.30), but statistical significance was not reached. Finally, cross-analysis between polymorphisms of the three studied genes revealed significant interaction between TLR2 +597 and TLR4 +4434 SNPs towards protection against PTB (pc = 0.036), suggesting that the functionally relevant TLR4 +4434 SNP may act synergistically with TLR2 SNPs.
TLR2 and TLR4 interaction and a specific VDR haplotype influence protection against PTB in Moroccans patients.
Abstract Nasopharyngeal carcinoma (NPC) is a complex multifactorial disorder involving both genetic and environmental factors. Polymorphisms of genes encoding nitric oxide synthase (NOS) and ...antioxidant glutathione-S transferases (GSTs) have been associated with various tumors. We examined the combined role of NOS3, NOS2 and GST polymorphisms in NPC risk in Tunisians. We found that NOS3−786C allele and −786 CC genotype, NOS3+894T allele and +894 GT+TT genotypes, NOS2−277 G allele and −277 GG genotype, and GSTT1 del/del genotype, are more prevalent in NPC patients as compared to healthy controls. Our results suggest that genetically driven dysfunction in red–ox stress pathway could augment the risk in NPC-susceptible individuals.
Le syndrome de Sneddon est une entité rare qui associe un livédo pathologique et des manifestations neurologiques ischémiques récidivantes, exposant au risque de démence vasculaire. Son lien avec le ...péripartum est à préciser.
O.Z., 45ans, G4P3A1, sans facteurs de risque cardiovasculaire en dehors de la prise d’œstro-progestatifs et un BMI à 29kg/m2 présente en 1998 à 02 mois du péripartum, d’une grossesse menée à terme sans événements cardiovasculaires des crises convulsives généralisées (anomalies lentes thêta sur les régions temporales antérieures gauche objectivées à l’EEG) stabilisées par un traitement antiépileptique (tégrétol LP 400mg). En 2007 à la 36e semaine d’aménorrhée d’une 4e grossesse elle présente une aphasie motrice de Broca, précédée par des céphalées en casque, sans signes déficitaires ni d’HIC ni d’éclampsie ce qui justifie l’extraction fœtale par voie haute. La patiente note la majoration d’un livedo racemosa, l’examen neurologique retrouve des troubles mnésiques, un syndrome pyramidal unilatéral et l’IRM cérébrale objective des micro-lacunes ischémiques du noyau caudé gauche et cérébelleux droit associées à une lésion temporo-occipito-pariétale gauche séquellaire. L’exploration cardio-vasculaire est sans anomalies. Le bilan d’auto-immunité (facteurs antinucléaires, anticorps antiphospholipides) est négatif. L’évolution est favorable sous anti-agrégants plaquettaires et immunomodulateurs (antipaludéens de synthèse : hydroxychloroquine)
L’âge jeune de la patiente et l’association de signes cutanés à type de livedo racemosa et d’AVC ischémiques cérébraux récurrents et du fait de l’absence tout facteur de risque cardiovasculaire (HTA, diabète, dyslipidémie, valvulopathie emboligéne, artérite inflammatoire, tabac) hormis la contraception oralae, l’absence d’une pathologie vasculaire placentaire (HELLP syndrome, éclampsie) le diagnostic syndrome de Sneddon (SS) est retenu.
Le SS constitue une cause rare d’AVC du péripartum avec un risque maternofœtal. Le traitement préventif est empirique et tend à prévenir l’installation des troubles cognitifs imputables aux AVC ischémiques récurrent.
Introduction
Inborn errors of immunity (IEI) represent a heterogeneous large group of genetic disorders characterized by susceptibility of affected individuals to recurrent infections, ...autoimmune/inflammatory diseases, allergy, and malignancy. We aimed to report for the first time the Algerian registry for IEI in children.
Methods
We described the characteristics of IEI in Algerian children from the data collected in the Algerian registry for IEI between 1985 and 2021.
Results
Over a period of 37 years, we included 887 children (530 male, 59.6%) with a mean age at diagnosis of 3.23 years and a mean diagnosis delay of 2 years. The prevalence rate was estimated at 1.97/100,000 inhabitants or 5.91/100,000 children. The parental consanguinity was found in 52.6%. The most prevalent category was combined immunodeficiencies (CID) (35.5%), followed by predominantly antibody deficiencies (24.5%) and CID with syndromic features (18.3%). The most predominant diseases were severe CID (134 cases), MHC II deficiency (99 cases), agammaglobulinemia (82 cases), common variable immunodeficiency (78 cases), hyper IgE syndromes (61 patients), ataxia-telangiectasia (46 patients), Wiskott-Aldrich syndrome (40 patients) and chronic granulomatous disease (39 cases). The clinical presentation was dominated by lower respiratory tract infections (69%), failure to thrive (38.3%), and chronic diarrhea (35.2%). Genetic analysis was performed in 156 patients (17.6%). The global mortality rate was 28.4% mainly caused by CID.
Conclusion
This is the first report of the Algerian registry for IEI in children. Data is globally similar to that of the Middle East and North African (MENA) registries with high consanguinity, predominance of CID, and significant mortality. This registry highlights the weak points that should be improved in order to provide better patient care.
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