BackgroundPeach allergy represents a significant clinical problem in Mediterranean populations, yet molecular characterization remains limited in North African countries. This study provides the first comprehensive analysis of peach sensitization patterns in Tunisia using component-resolved diagnostics.ObjectiveTo characterize molecular sensitization profiles to peach allergen components, correlate these with clinical manifestations, and evaluate predictive biomarkers in a Tunisian cohort.MethodsA retrospective study was conducted including 63 patients referred for suspected peach allergy to the Pasteur Institute of Tunisia between March 2022 and March 2025. After application of exclusion criteria, 49 patients were included in the final analysis. Total and specific IgE levels were measured using ImmunoCAP® technology. Component-resolved diagnostics targeted rPru p 1, rPru p 3, rPru p 4, and rPru p 7. Reaction severity was assessed using oFASS-3. Statistical analyses included correlation studies and ROC curve analysis.ResultsThirty-eight patients (77.5%) demonstrated peach allergy with median age 10 years [7-14]. Clinical manifestations included urticaria (86.6%), angioedema (39.4%), respiratory symptoms (rhinitis 42.1%, bronchospasm 23.6%), oral allergy syndrome (32.4%), and anaphylaxis (10.5%). Pru p 3 was predominant (84.2% of patients, median 1.215 kUA/L). Pru p 7, Pru p 1, and Pru p 4 sensitization occurred in 10.5%, 7.8%, and 2% respectively. Peach-specific IgE predicted Pru p 3 sensitization with 100% sensitivity and 66.7% specificity (cut-off 0.23 kUA/L). Strong correlation existed between peach-specific IgE and Pru p 3 levels (ρ = 0.942). No associations were identified between biomarkers and clinical severity.ConclusionsPeach allergy in Tunisia follows the Mediterranean phenotype with predominant Pru p 3 sensitization and significant clinical severity. These findings establish the molecular foundation for evidence-based diagnosis while highlighting the need for region-specific therapeutic approaches.

Muscle biopsy (MB) is an important tool to help differentiate idiopathic inflammatory myopathies (IIMs) from hereditary muscular diseases (HMDs). The usefulness of immunohistochemical stains of the major histocompatibility complex class I and the membrane attack complex are controversial, as both may be identified in some HMDs. More sensitive markers of IIMs have recently been used, such as myxovirus resistance A (MxA), a type I interferon-inducible protein. We selected skeletal MB samples from 81 patients diagnosed with IIM and HMD harbouring overt inflammatory infiltrates on their MBs in the period between March 2022 and September 2024. Two groups were identified: the IIM group (46 cases) and the HMD group (35 cases). We characterized and compared the patterns of MxA protein expression among the two groups. In the IIM group, positive sarcoplasmic MxA expression was detected on the myofibres of 10 patients (24%), among whom were eight dermatomyositis patients. In the HMD group, we did not identify any sarcoplasmic positivity. However, five patients (14%) showed positive labelling restricted to the sarcolemmal membrane, including non-necrotic or regenerating fibres. Our study demonstrates the value of MxA for increasing dermatomyositis diagnostic accuracy and suggests the potential role of interferon type I in the pathophysiology of HMD.

Myelin oligodendrocyte glycoprotein antibody disease (MOGAD) and anti-N-methyl-D- aspartate receptor (NMDAR) encephalitis pediatric cases are especially challenging due to phenotypic variability, limited literature, and the absence of standardized treatment protocols. We present the first documented African case of pediatric MOG and NMDAR overlapping syndrome (MNOS), with a review of all pediatric MNOS cases reported thus far in the literature. A previously healthy seven-year-old boy developed rapid-onset sleep disturbances, neuropsychiatric symptoms, multiple cranial nerve palsies, and hyperkinetic movements. Serological and cerebrospinal fluid (CSF) analyses confirmed dual positivity for anti- MOG and anti- NMDAR antibodies. The patient responded favorably to first line immunotherapy with intravenous immunoglobulin and corticosteroids, showing marked clinical improvement by the six-month follow-up. A corticosteroid taper was initiated thereafter. At fourteen-month follow-up, he had a second episode with a MOGAD- associated cerebral cortical encephalitis phenotype. Antibody screening confirmed persistent dual positivity for both anti-NMDAR and anti-MOG antibodies. The clinical outcome was favorable following first-line immunotherapy combined with oral immunosuppressants. This case highlights the uniqueness of this entity, where antibody dynamics are closely tied to the clinical course.

BackgroundThe frequency of extractable nuclear antigen (ENA) seropositivity in patients with negative antinuclear antibodies (ANA) by indirect immunofluorescence (IIF) remains insufficiently characterized. We aimed to estimate the frequency of ENA seropositivity among ANA-IIF–negative individuals (ENA+/IIF−), and to identify associated clinical and methodological determinants. MethodsA systematic search of PubMed, EMBASE, Web of Science, and Scopus was conducted for studies published up to January 31, 2025. Studies evaluating ENA seropositivity in ANA-IIF–negative patients using HEp-2 or HEp-2000 substrates were included. Meta-analysis was performed using the Freeman–Tukey double arcsine transformation and random-effects models.ResultsTwenty-eight studies, comprising 33 distinct patient groups and 28,552 ANA-IIF–negative samples, were included. The pooled proportion of ENA+/IIF− was 14.1% (95% CI: 10%–18.7%), with substantial heterogeneity (I² = 99%). Subgroup analysis demonstrated significant variation according to clinical indication: 1.4% (95% CI: 1.1%–1.9%) in unspecified indications, 8.1% (95% CI: 6%–10.5%) in suspected connective tissue disease (CTD), and 44.1% (95% CI: 32.3%–54.6%) in confirmed CTD (p < 0.0001). Multivariable meta-regression identified the IIF cut-off dilution, anti-SSA/Ro antibodies, and anti-tRNA synthetase antibodies as significant determinants of ENA+/IIF− frequency.DiscussionThis meta-analysis confirmed that ENA seropositivity is not uncommon in ANA-IIF–negative individuals, and it varies according to clinical context. A negative ANA-IIF result does not reliably exclude CTD, particularly in patients with strong clinical suspicion of CTD. These findings support a targeted, clinically driven ENA testing strategy, especially in conditions such as Sjögren syndrome and inflammatory myopathies.Systematic Review Registrationhttps://www.crd.york.ac.uk/PROSPERO/view/, identifier CRD420250654499.

Cow's milk protein allergy (CMPA) represents a major health concern in Tunisia, with diagnostic challenges influencing disease prognosis. Molecular allergen testing has emerged as a valuable tool to enhance diagnostic accuracy and predict disease persistence. This study aims to characterize the clinical and epidemiological features of CMPA in a Tunisian population, with a particular focus on the role of molecular allergens in assessing disease chronicity. A retrospective analysis was conducted on 262 cases of IgE-mediated CMPA diagnosed at the Pasteur Institute of Tunis between 2020 and 2023. Sensitization to molecular allergens was assessed using ImmunoCAP (Phadia 100). CMPA symptoms predominantly manifested in infancy (94%, 246/262), with a male predominance (sex ratio: 1.6). Acute reactions were the most frequent presentation (69.9%, 79/113), and polysensitization was common (81%, 212/262), particularly to β-lactoglobulin. Spontaneous resolution occurred in approximately 33% of cases (29/87), with a mean age of 3 years and 8 months. Persistent CMPA was significantly associated with elevated IgE levels to whole milk, β-lactoglobulin, and casein (p < 0.05). ROC curve analysis identified predictive thresholds for disease persistence, including 4.2 kU/L for whole milk-specific IgE and 0.37 kU/L for casein-specific IgE (p = 0.006). Molecular allergen testing improves CMPA diagnosis and offers critical prognostic insights. The identification of IgE thresholds may facilitate early risk stratification and guide personalized management strategies.

BackgroundHypocomplementemic urticarial vasculitis (HUV) syndrome is a rare form of small-vessel vasculitis characterized by a heterogeneous spectrum of clinical and biological findings. It is typically marked by chronic urticarial eruptions, hypocomplementemia and histopathological evidence of leukocytoclastic vasculitis. It may also involve multiple organ systems, with frequent articular, gastrointestinal, renal, and other systemic manifestations. The differential diagnosis with other systemic autoimmune diseases, particularly systemic lupus erythematosus (SLE), is often challenging due to their frequent association and the blurred boundaries between these entities.Case presentationWe report the case of a 34-year-old Tunisian man with an association of HUV and SLE. The diagnosis of SLE was established according to the 2019 European League Against Rheumatism (EULAR) criteria, based on the combination of inflammatory polyarthralgia, lymphopenia, a high titer of anti-nuclear antibodies, specific anti-Sm and anti-DNA antibodies, and consumption of C3 and C4 complement fractions. The diagnosis of HUV was made based on the presence of two major criteria: chronic urticaria and hypocomplementemia, along with four minor criteria: leukocytoclastic vasculitis, recurrent abdominal pain, episcleritis, and the presence of anti- C1q antibodies.ConclusionHUV and SLE share key clinical, immunological, and pathophysiological features, suggesting that they may lie along the same spectrum of autoimmune diseases. Their association, as seen in our patient, has been described in the literature. This overlap may result in more severe disease and requires close clinical follow-up.

Anti-3-hydroxy-3-methylglutaryl-coenzyme A reductase (anti-HMGCR) myopathy is a rare idiopathic inflammatory myopathy characterized by severe muscle damage and minimal extra-muscular involvement. This report presents the first documented case of severe, treatment-resistant HMGCR-myopathy in a Tunisian and North African patient. A 43-year-old man with no significant medical history experienced progressive muscle weakness over one year, leading to difficulty walking. Examination revealed pronounced proximal muscle weakness, particularly in the lower limbs, with significant quadriceps atrophy. Laboratory results indicated elevated Creatine Kinase (CK) levels at 10000 UI/l and Lactate dehydrogenase (LDH) at 400 UI/l. Electromyography confirmed myogenic damage, and muscle biopsy revealed extensive muscle necrosis and regeneration with moderate inflammatory infiltrates. Screening for anti-HMGCR antibodies was positive. Initial treatment with high-dose prednisone showed a good response but led to flares upon tapering. Subsequent treatment with methotrexate, azathioprine, and rituximab resulted in partial clinical and biological improvement. This case underscores the challenges in diagnosing and managing anti-HMGCR myopathy due to limited awareness and access to testing.

Shrimp allergy has emerged as a growing health concern in Tunisia, likely due to changing dietary habits. This study aimed to characterize the clinical features of shrimp-allergic patients and investigate potential cross-reactivity with house dust mites (HDMs) and snails using in vitro diagnostic methods. Thirty-one patients with a self-reported history of shrimp allergy were referred to the Clinical Immunology Department of the Pasteur Institute of Tunis. Total IgE and Serum-specific IgE (sIgE) levels to shrimp, snail, and HDMs, as well as recombinant allergens rPen a1 and rDer p10, were measured using the ImmunoCAP® immunoassay. The study population consisted mainly of young adults [mean age: 15.5 years (10–27.2)], with a male-to-female ratio of 1.4. The most common symptoms were oropharyngeal pruritus and urticaria. Shrimp allergy was confirmed in 54.8% of patients, with a median sIgE titer of 0.18 [0.03–28.8] kUA/L. Among these patients, 58.8% exhibited cross-reactivity, predominantly with snails [median sIgE: 3.07 (0.04–16.85) kUA/L]. Among shrimp-allergic patients, 70.5% tested positive for rPen a1 [median sIgE: 28.42 (5.78–51.05) kUA/L], while 58.8% were positive for rDer p10 (median sIgE: 0.56 [5 × 10−5–87.95] kUA/L). The median total IgE level was 297 [158.6–475] IU/ml, significantly higher in shrimp-allergic patients (p = 0.005). The median shrimp sIgE/total IgE ratio was 0.001 [0–0.069], also significantly elevated in shrimp-sensitized individuals (p = 0.005). Multivariable analysis showed significant correlations between total IgE and shrimp sIgE, rPen a1, and rDer p10 levels (p = 0.043, p = 0.045, p = 0.043, respectively), while no correlation was found with d1 or snail sIgE after adjusting for age. rDer p10 and f24 were the strongest predictors of sIgE to snail, with standardized coefficients of 8.785 and −5.028, respectively. However, these associations did not reach statistical significance. This study underscores the critical role of tropomyosin as a primary allergen in shrimp allergy in Tunisia, highlighting its importance in immunodiagnosis and its strong association with HDMs and snail sensitization. Further research is needed to explore HDMs sensitization in patients who are negative for rPen a1 and rDer p10.

The interplay between the cytokine network and antipsychotic treatment in schizophrenia remains poorly understood. This study aimed to investigate the impact of psychotropic medications on serum levels of IFN-γ, IL-4, TGF-β1, IL-17, and BAFF, and to explore their relationship with psychopathological features. We recruited 63 patients diagnosed with schizophrenia in the acute phase, all of whom were either drug-naïve or had been drug-free for at least three months. Serum levels of IL-4, IFN-γ, TGF-β1, IL-17, and BAFF were measured at baseline and after six months of antipsychotic treatment. The severity of symptoms was assessed using the Brief Psychiatric Rating Scale (BPRS), the Scale for the Assessment of Positive Symptoms (SAPS), and the Scale for the Assessment of Negative Symptoms (SANS). Fifty-two patients completed the six-month follow-up for immunoassay analysis. Antipsychotic treatment led to a significant decrease in serum levels of IFN-γ, TGF-β1, and IL-17, alongside a significant increase in BAFF levels. Changes in IFN-γ were positively correlated with SANS scores and negatively correlated with Global Assessment of Functioning (GAF) scores. Changes in TGF-β1 were negatively correlated with GAF scores. Changes in BAFF were negatively correlated with SAPS scores. Multivariable regression models were used to explore the association between cytokine level changes (IL-17, BAFF, IFN-γ, and TGF-β1) and independent variables, including demographic (gender, age), behavioral (tobacco use), clinical (schizophrenia type, disease course, date of onset, prior treatment), and biological (C-reactive protein (CRP), erythrocyte sedimentation rate (ESR)) factors, as well as standardized assessment scores. No significant associations were found, except for a significant negative correlation between TGF-β1 changes and GAF scores, as well as a positive correlation with age. Interestingly, advanced statistical analyses revealed that only changes in IL-17 and BAFF levels were significantly associated with antipsychotic treatment. Our findings suggest that antipsychotic drugs exert both pro- and anti-inflammatory effects on the cytokine network. The observed modulation of IL-17 and BAFF highlights their potential as future therapeutic targets in schizophrenia.

Introduction:Anti-neutrophil cytoplasmic antibodies (ANCAs) have been reported in systemic lupus erythematosus (SLE). Their clinical significance remains unclear especially in the African populations. This study aimed to assess the prevalence, antigenic targets, and clinical correlations of ANCAs in SLE patients in a Tunisian (North African) cohort. Methods:We conducted a cross-sectional case-control study involving 30 patients with systemic lupus erythematosus (SLE) and 30 healthy controls. Blood samples were screened for antineutrophil cytoplasmic antibodies (ANCAs) using indirect immunofluorescence (IIF) (FA 1201-1005-13, Euroimmun®). Enzyme-linked immunosorbent assay (ELISA) (Euroimmun®) was performed on IIF-positive samples to assess six ANCA antigenic targets: proteinase 3, lactoferrin, myeloperoxidase, elastase, cathepsin G, and bactericidal/permeability-increasing protein (BPI). Clinical and immunological evaluations were conducted for all SLE patients at the time of the study. No ANCA- associated vasculitis-SLE overlap cases were identified. Results and discussion:ANCAs were detected in 16 of 30 SLE patients (53%) and in 1 of 30 healthy controls (3%). Among the ANCA-positive patients, nine showed reactivity to lactoferrin, while the antigenic target remained undetermined in 7 cases. The median SLEDAI-2K score at inclusion was 8 [1.75-12]. In univariate study, ANCA positivity was significantly associated with acute cutaneous manifestations (p=0.021), lupus nephritis (p=0.001), as well as use of glucocorticoids (p=0.014) and mycophenolate mofetil (p=0.009). Besides, it was associated with lower C3 (p=0.0036) and C4 (p=0.0032) titers and higher anti-dsDNA titers (p<0.0001). In multivariate analysis, ANCA positivity was correlated to anti-ds DNA (p=0.008). When comparing anti-LF positive and anti-LF negative patients, univariate analysis found an association with articular involvement (p=0.011), renal activity index (p=0.036) and ELISA titers (p=0.0004). ANCAs were frequent in our SLE cohort, with lactoferrin as the only identifiable antigenic target, unlike previous reports, which suggests a role to ethnicity and environment components. Their presence was associated with higher disease activity and more severe renal involvement.

Post-COVID syndrome (PCS) is characterized by a polymorphism of symptoms with hypothetical pathophysiological mechanisms. Here, we aimed to analyze the profile of inflammatory cytokines in patients with PCS and to study the relationship between this profile, the clinical symptoms as well as the endothelial function in PCS. Our analytical study involved all eligible patients (n = 66) with PCS included from April 2021 to December 2021. The serum concentration of cytokines IFN-γ, IL-1α, IL-1β, IL-6, IL-8, IL-10, IL-12p70, IL-27, IP-10, MCP-1 and TNF-α was quantified by flow cytometry. Endothelial function was explored by assessing microvascular flow and reactivity using thermal probes. A comparative study was carried out according to the presence of each PCS symptom. The average age of our patients was 55.9 ± 16.2 years. The sex ratio was 0.69. Forty-one patients (62

Background: Allogeneic hematopoietic stem cell transplantation (ASCT) induces acquired immunodeficiency, potentially altering vaccine response. Herein, we aimed to explore the clinical tolerance and the humoral and cellular immune responses following anti-SARS-CoV-2 vaccination in ASCT recipients. Methods: A prospective, non-randomized, controlled study that involved 43 ASCT subjects and 31 healthy controls. Humoral response was investigated using the Elecsys® test anti-SARS-CoV-2. Cellular response was assessed using the QFN® SARS-CoV-2 test. The lymphocyte cytokine profile was tested using the LEGENDplex™ HU Th Cytokine Panel Kit (12-plex). Results: Adverse effects (AE) were observed in 69% of patients, encompassing pain at the injection site, fever, asthenia, or headaches. Controls presented more side effects like pain in the injection site and asthenia with no difference in the overall AE frequency. Both groups exhibited robust humoral and cellular responses. Only the vaccine transplant delay impacted the humoral response alongside a previous SARS-CoV-2 infection. Noteworthily, controls displayed a Th1 cytokine profile, while patients showed a mixed Th1/Th2 profile. Conclusions: Pfizer-BioNTech® anti-SARS-CoV-2 vaccination is well tolerated in ASCT patients, inducing robust humoral and cellular responses. Further exploration is warranted to understand the impact of a mixed cytokine profile in ASCT patients.

Background/Objectives: Schizophrenia (SZ) is a complex psychiatric disorder with increasing evidence pointing to an autoimmune component, including the presence of antiphospholipid antibodies (aPLs). This study aims to assess the prevalence of anticardiolipin (aCL) and anti-beta-2 glycoprotein I (aβ2GPI) antibodies, particularly the IgG, IgA, and IgM isotypes, in drug-free SZ patients compared to healthy controls, and explore their possible involvement in the disease’s pathophysiology. Methods: Eighty SZ patients meeting DSM-IV criteria were recruited, along with 80 matched healthy controls. Serum samples were analyzed using enzyme-linked immunosorbent assays (ELISA) to quantify IgG, IgA, and IgM isotypes of aCL and aβ2GPI. Results: SZ patients exhibited significantly higher levels of aCL-IgM and aCL-IgA (p < 0.05), as well as elevated aβ2GPI-IgA (22.5%, p < 0.001), compared to controls. No significant differences were observed in the aCL-IgG isotype. Interestingly, 72% of aPL-positive SZ patients were positive for aβ2GPI-IgA, with some also co-expressing multiple isotypes, suggesting a potential link between SZ and antiphospholipid syndrome (APS). Conclusions: This study is the first to report a high prevalence of aCL-IgA and aβ2GPI-IgA in SZ patients, highlighting a possible autoimmune involvement in the disease. The presence of multiple aPL isotypes, particularly IgA, suggests a need for further investigation into their role in SZ pathogenesis and their potential association with APS.

(1) Background: This study aimed to compare the immunogenicity of the mix-and-match CoronaVac/BNT162b2 vaccination to the homologous CoronaVac/CoronaVac regimen. (2) Methods: We conducted a simple-blinded randomized superiority trial to measure SARS-CoV-2 neutralization antibodies and anti-spike receptor binding domain (RBD) IgG concentrations in blood samples of participants who had received the first dose of CoronaVac vaccine followed by a dose of BNT162b2 or CoronaVac vaccine. The primary endpoint for immunogenicity was the serum-neutralizing antibody level with a percentage of inhibition at 90% at 21–35 days after the boost. A difference of 25% between groups was considered clinically relevant. (3) Results: Among the 240 eligible participants, the primary endpoint data were available for 100 participants randomly allocated to the mix-and-match group versus 99 participants randomly allocated to the homologous dose group. The mix-and-match regimen elicited significantly higher levels of neutralizing antibodies (median level of 96%, interquartile range (IQR) (95–97) versus median level of 94%, IQR (81–96) and anti-spike IgG antibodies (median level of 13,460, IQR (2557–29,930) versus median level of 1190, IQR (347–4964) compared to the homologous group. Accordingly, the percentage of subjects with a percentage of neutralizing antibodies > 90% was significantly higher in the mix-and-match group (90.0%) versus the homologous (60.6%). Interestingly, no severe events were reported within 30 days after the second dose of vaccination in both groups. (4) Conclusions: Our data showed the superiority of the mix-and-match CoronaVac/BNT162b2 vaccination compared to the CoronaVac/CoronaVac regimen in terms of immunogenicity, thus constituting a proof-of-concept study supporting the use of inactivated vaccines in a mix-and-match strategy while ensuring good immunogenicity and safety.

Hypotheses regarding an immune-cytokine basis of schizophrenia have been postulated with controversial findings and a lack of data related to many cytokines. The aim of this study was to assess serum levels of Interferon-γ (IFN-γ), Interleukin-4 (IL-4), Transforming Growth Factor-β (TGF-β), Interleukin-17 (IL-17) and B-cell Activating Factor (BAFF) in schizophrenic patients and to determine correlations between cytokine levels and clinical parameters. Serum cytokine levels were measured with ELISA techniques in 60 neuroleptic-free patients on acute phase of the disease (BPRS≥40) and 28 healthy controls matched for age and sex. Current symptoms were assessed with Brief Psychiatric Rating Scale (BPRS), Positive and Negative Syndrome Scale (PANSS), Scale for the Assessment of Positive Symptoms (SAPS) and Scale for the Assessment of Negative Symptoms (SANS). No significant difference was found between patients and controls regarding IFN-γ serum levels. IL-4 was not detected in both groups. Patients exhibited significantly higher IL-17 and lower BAFF serum levels. IL-17 and BAFF levels were negatively correlated in schizophrenic patients. SANS global score was negatively correlated with IL-17 and positively correlated with IFN-γ serum levels. These results argue against the involvement of Th1 or Th2 population cells in schizophrenia. IL-17 and BAFF could be valuable markers for schizophrenia.

Objective: This study was designed to review the effect of chronic aluminium exposure on interleukin-6 (IL-6) secretion in the posterior brain and test the putative modulating effect of fenugreek seeds.Methods: Female Wistar rats were divided into four groups: control; AlCl3 during 5 months (500 mg/kg body weight, intragastric for 1 month then 1600 ppm via the drinking water); AlCl3 plus fenugreek seed powder (FSP) (5%) during the last 2 months and FSP alone.Results: Oral administration of aluminium chloride during 5 months caused hypoproduction of IL-6 together with a decrease in GFAP reactivity and an alteration of antioxidant status in the posterior brain. On the other hand, fenugreek seeds supplementation was able to enhance IL-6 expression, re-increase GFAP reactivity, and modulate the pro-oxidant-related effect.Discussion: In the context of recent researches, IL-6 hypoproduction in the posterior brain could be a novel mechanism of Al chronic toxicity with a direct effect on glial cells. Using FSP as a diet supplement could offer a neuroprotective effect against Al toxicity. This could be mediated by astroglial cells protection, antioxidant and immunomodulatory actions.