Follicular dendritic cell accessory activity crosses MHC and species barriers

Productive follicular dendritic cell (FDC)-B cell interactions appear to involve critical ligand-receptor interactions. Immune complexes (IC) on FDC activate complement and provide FDC with a complement-derived CD21 ligand (CD21L), which bind CD21, while antigen in the IC binds on the B cell-BCR. Further, FDC-FcgammaRIIB binds Fc regions of antibodies in IC and reduces coligation of BCR and FcgammaRIIB minimizing an inhibitor of B cell activation. Given that Fc receptors and complement receptors bind immunoglobulins and complement fragments of other species, we reasoned that FDC accessory activity should cross MHC and species barriers. This prediction was tested using memory lymphocytes from OVA-immune mice and TT-immune humans in combination with FDC from murine lymph nodes and human tonsils. Human and murine FDC converted IC into potent immunogens (specific antibody increased from background to thousands of ng / ml). MHC barriers did not restrict this activity and human FDC worked with murine lymphocytes and murine FDC worked with human lymphocytes. Furthermore, stimulation via MHC-dependent allogeneic or zenogeneic mechanisms did not promote antibody production by FDC. Polyclonal responses stimulated by lipopolysaccharide and pokeweed mitogen were also promoted (10 - 100-fold) and anti-CD21 blocked FDC activity. These results substantiate the hypothesis that FDC are necessary for strong recall responses and that FDC-CD21L is critical.     

Synthesis and pharmacological evaluation of pyrazolopyrimidopyrimidine derivatives: anti-inflammatory agents with gastroprotective effect in rats

We report the synthesis of new anti-inflammatory 1,7-dihydropyrazolo[3′,4′:4,5]pyrimido[1,6-a]pyrimidine 5 from aminocyanopyrazole. All compounds were characterized by physical, chemical and spectral studies. Preliminary pharmacological evaluation of the resulting products showed that compounds 5a, b, f (50–100 mg/kg, i.p) are active anti-inflammatory agents in carrageenan-induced rat paw oedema assay, and their effects are comparable to that of acetylsalicylic–lysine (300 mg/kg, i.p.), used as a reference drug. The nature of substituent (Y, R₃) had a pronounced effect on the anti-inflammatory activity. Studies of structure–activity relationships have led to selection of compound ethyl-3,5-dimethyl-7-imino-N ¹-phenyl-1,7-dihydropyrazolo[3′,4′:4,5]pyrimido[1,6-a]pyrimidine-6-carboxylate, 5f which exhibited the most potent anti-inflammatory activity. In addition, the compounds 5a, b, f showed a significant gastroprotective effect against HCl/EtOH-induced gastric ulcer.     

Molecular Epidemiology of SARS-CoV-2 in Tunisia (North Africa) through Several Successive Waves of COVID-19

Documenting the circulation dynamics of SARS-CoV-2 variants in different regions of the world is crucial for monitoring virus transmission worldwide and contributing to global efforts towards combating the pandemic. Tunisia has experienced several waves of COVID-19 with a significant number of infections and deaths. The present study provides genetic information on the different lineages of SARS-CoV-2 that circulated in Tunisia over 17 months. Lineages were assigned for 1359 samples using whole-genome sequencing, partial S gene sequencing and variant-specific real-time RT-PCR tests. Forty-eight different lineages of SARS-CoV-2 were identified, including variants of concern (VOCs), variants of interest (VOIs) and variants under monitoring (VUMs), particularly Alpha, Beta, Delta, A.27, Zeta and Eta. The first wave, limited to imported and import-related cases, was characterized by a small number of positive samples and lineages. During the second wave, a large number of lineages were detected; the third wave was marked by the predominance of the Alpha VOC, and the fourth wave was characterized by the predominance of the Delta VOC. This study adds new genomic data to the global context of COVID-19, particularly from the North African region, and highlights the importance of the timely molecular characterization of circulating strains.     

Distribution of HLA-B27 and its alleles in patients with reactive arthritis and with ankylosing spondylitis in Tunisia

The purpose of the present study is to investigate the frequency of HLA-B27 and its alleles in reactive arthritis (ReA) and in ankylosing spondylitis (AS) in Tunisia. HLA-B27 alleles were typed by PCR amplification with sequence-specific primers. We studied 17 patients with ReA associated with urethritis or with gastrointestinal infection; 42 HLA-B27-positive patients with AS and 100 healthy controls. Eleven ReA patients (67.7%) were HLA-B27 positive. There was an increased frequencies of HLA-B27 (P = 7.76 × 10⁻¹², OR = 59.30) and a moderate increase of HLA-B51 (P = 0.015; OR = 4.91) alleles in ReA patients when compared with healthy controls. Four B27 subtypes were identified: B*2702, 05, 09 and B*2712. The distribution of these alleles in the ReA patients was 37.5% for B*2702 and B*2705. Only these two subtypes were detected in 18 (42.8%) and 24 (57.1%), respectively, of the AS patients. B*2709 and B*2712 were relatively rare in ReA patients and were identified in one case each. Our results showed a restricted number of HLA-B27 subtypes associated with ReA and AS. B*2702 and 2705 were common in ReA and AS patients.     

Ventilatory mechanics and alveolo-capillary diffusion in diabetes

In order to appreciate the repercussion of diabetes on the respiratory function, we measured the pulmonary volumes, the ventilatory flows, the airways resistances (Raw) and the diffusing capacity for the carbon monoxide (DLCO) of 49 diabetes distributed into 27 IDDM and 22 NIDDM aged from 15 to 56 years, compared to 31 control subjects. We found a significant decrease in the total pulmonary capacity (TCL), the vital capacity (VC), the inspiratory capacity (IC), the ventilatory flows and the DLCO. The decrease of the VC and the FEV1 will be more marked in the IDDM. The decrease of the DLCO will be more pronounced within masculine sex, it seems to be correlated with the duration of diabetes and more impaired if a diabetic nephropathy is associated especially in IDDM. Our results suggest that in the diabetes evolution, the lung is among the target organs in the degenerative complications. The respiratory tests reflect the pulmonary reach in the diabetes and provides important perspectives in the following.     

Engagement of transferrin receptor by polymeric IgA1: evidence for a positive feedback loop involving increased receptor expression and mesangial cell proliferation in IgA nephropathy

IgA nephropathy (IgAN), the most common primary glomerulonephritis in the world, is characterized by IgA immune complex-mediated mesangial cell proliferation. The transferrin receptor (TfR) was identified previously as an IgA1 receptor, and it was found that, in biopsies of patients with IgAN, TfR is overexpressed and co-localizes with IgA1 mesangial deposits. Here, it is shown that purified polymeric IgA1 (pIgA1) is a major inducer of TfR expression (three- to four-fold increase) in quiescent human mesangial cells (HMC). IgA-induced but not cytokine-induced HMC proliferation is dependent on TfR engagement as it is inhibited by both TfR1 and TfR2 ectodomains as well as by the anti-TfR mAb A24. It is dependent on the continued presence of IgA1 rather than on soluble factors released during IgA1-mediated activation. In addition, pIgA1-induced IL-6 and TGF-beta production from HMC was specifically inhibited by mAb A24, confirming that pIgA1 triggers a TfR-dependent HMC activation. Finally, upregulation of TfR expression induced by sera from patients with IgAN but not from healthy individuals was dependent on IgA. It is proposed that deposited pIgA1 or IgA1 immune complexes could initiate a process of auto-amplification involving hyperexpression of TfR, allowing increased IgA1 mesangial deposition. Altogether, these data unveil a functional cooperation between pIgA1 and TfR for IgA1 deposition and HMC proliferation and activation, features that are commonly implicated in the chronicity of mesangial injuries observed in IgAN and that could explain the recurrence of IgA1 deposits in the mesangium after renal transplantation.     

Effect of triple antiretroviral therapy on Tunisian AIDS profile: study of 139 cases

We report a retrospective study to estimate highly active antiretroviral therapy (HAART) effect in 139 HIV infected patients. Four criteria are studied: prevalence of opportunistic infections, CD4 cell count evolution, viral load progression and mortality. Gastrointestinal side effects are the most common clinical adverse reaction (61.1 percent), and hematological side effects are the most common biological adverse reaction (61.2 percent). During the 22.8 months (3 months to 6 years) follow-up average period, CD4 cell counts remained above 500 per cubic millimeter in only 25.8 percent of cases, while 63.5 percent of patients had a viral load below 400 copies per milliliter. During the study on patients receiving HAART, opportunistic infections appeared in 17.3 percent of cases (24 cases) and mortality in 6.4 percent of cases.     

Male gonococcal urethritis in the region of Sfax (1996-2000)

The sexually transmitted infections pose a real public health problem, mainly in developing countries. In Tunisia, the epidemiological state is not precise. The objective of our study was to determine the sociological, epidemiological and bacteriological characteristics of gonococcal urethritis in the area of Sfax. The study was performed on all patients attending at the CNSS of Sfax for urethritis for 5 years, from 1996 to 2000. A urethral swab was carried out for each patient with a classic bacteriological exam. 256 cases were collected. The mean age was 29.7 years. 74.3% were workers. The direct exam was positive in 51.2% of cases and the culture enabled us to isolate 72 strains, of which 15.5% were productive of beta-lactamase and 23.9% were resistant to tetracyclin. There was no resistance to pristinamycin, ofloxacin nor spectinomycin.