Human Monkeypox: A Comprehensive Overview of Epidemiology, Pathogenesis, Diagnosis, Treatment, and Prevention Strategies.

Monkeypox virus (MPXV) is an emerging zoonotic virus that belongs to the Orthopoxvirus genus and presents clinical symptoms similar to those of smallpox, such as fever and vesicular-pustular skin lesions. However, the differential diagnosis between smallpox and monkeypox is that smallpox does not cause lymphadenopathy but monkeypox generates swelling in the lymph nodes. Since the eradication of smallpox, MPXV has been identified as the most common Orthopoxvirus to cause human disease. Despite MPXV being endemic to certain regions of Africa, the current MPXV outbreak, which began in early 2022, has spread to numerous countries worldwide, raising global concern. As of the end of May 2023, over 87,545 cases and 141 deaths have been reported, with most cases identified in non-endemic countries, primarily due to human-to-human transmission. To better understand this emerging threat, this review presents an overview of key aspects of MPXV infection, including its animal reservoirs, modes of transmission, animal models, epidemiology, clinical and immunological features, diagnosis, treatments, vaccines, and prevention strategies. The material presented here provides a comprehensive understanding of MPXV as a disease, while emphasizing the significance and unique characteristics of the 2022 outbreak. This offers valuable information that can inform future research and aid in the development of effective interventions.

ICOS Gene Polymorphisms (IVS1 + 173 T/C and c. 1624 C/T) in Primary Sjögren's Syndrome Patients: Analysis of ICOS Expression.

Background: Primary Sjögren's syndrome (pSS) is a systemic autoimmune disease, which affects exocrine glands. T cell activation is a trigger mechanism in the immune response. Hyperreactivity of T cells and antibody production are features in pSS. ICOS can be critical in the pathogenesis of pSS. Methods: A total of 134 pSS patients and 134 control subjects (CS) were included. Genotyping was performed by PCR-RFLP. ICOS mRNA expression was quantified by real-time PCR, and CD4+ ICOS+ T cells were determined by flow cytometry. Results: The ICOS IVS1 + 173 T>C polymorphisms were not associated with susceptibility to pSS (p = 0.393, CI = 0.503−1.311). However, the c.1624 C>T polymorphism was associated with a reduction in the risk of development of pSS (p = 0.015, CI = 0.294−0.884). An increase in ICOS mRNA expression in patients was observed (3.7-fold). Furthermore, pSS patients showed an increase in membranal-ICOS expression (mICOS). High expression of mICOS (MFI) was associated with lymphocytic infiltration. Conclusions: The IVS1 + 173 polymorphism is not a genetic marker for the development of pSS, while c.1624 T allele was associated with a low risk. However, elevated mICOS expression in pSS patients with high lymphocytic infiltration was found. ICOS may have an important role in the immunopathogenesis of pSS and should be analyzed in T cell subsets in pSS patients as a possible disease marker.

Renal Tissue Expression of BAFF and BAFF Receptors Is Associated with Proliferative Lupus Nephritis.

Background: The B-cell activating factor (BAFF) controls the maturation and survival of B cells. An imbalance in this cytokine has been associated with systemic autoimmunity in SLE and lupus nephritis (LN). However, few investigations have evaluated the tissular expression of BAFF in LN. This study aimed to associate BAFF system expression at the tissular level with the proliferative LN classes. Methods: The analysis included eighteen kidney tissues, with sixteen LN (class III = 5, class IV = 6, class III/IV+V = 4, and class V = 1), and two controls. The tissular expression was evaluated with an immunochemistry assay. A Cytation5 imaging reader and ImageJ software were used to analyze the quantitative expression. A p-value < 0.05 was considered significant. Results: The expressions of BAFF, A proliferation-inducing ligand (APRIL), and their receptors were observed in glomerular, tubular, and interstitial zones, with BAFF being the most strongly expressed in the overall analysis. BAFF-Receptor (BR3), transmembrane activator and CALM interactor (TACI), and B-Cell maturation antigen (BCMA) displayed higher expressions in LN class IV in all zones analyzed (p < 0.05). Additionally, a positive correlation was found between APRIL, TACI, and BCMA at the glomerular level; BCMA and APRIL in the interstitial zone; and BR3, TACI, and BCMA in the tubule (p < 0.05). Conclusions: The expression of BAFF and BAFF receptors is mainly associated with LN class IV, emphasizing the participation of these receptors as an essential pathogenic factor in kidney involvement in SLE patients.

B-cell activating factor receptor expression is associated with germinal center B-cell maintenance.

B-cell activating factor (BAFF) is a major cytokine that regulates B-cell survival, maturation and differentiation through its binding with its receptors: BAFF receptor (BAFF-R), transmembrane activator and cyclophilin ligand interactor (TACI) and B-cell maturation antigen (BCMA). These receptors have been demonstrated to be involved in tertiary lymphoid structure formation; however, their role in germinal centers (GCs) has remained elusive. The aim of the present study was to determine the expression profiles of BAFF and its receptors in secondary lymphoid tissues. Tonsils resected due to chronic tonsillitis were used as lymphoid tissues. To confirm the presence of GCs identified based on their typical structure, CD21 antibody staining was employed. The expression of BAFF, BAFF-R, TACI and BCMA was assessed by immunohistochemistry. BAFF was highly expressed in all regions of the follicle, but the highest BAFF expression was detected in the mantle zone (MZ). A high expression of BAFF-R was observed on lymphocytes in the MZ in comparison with the other regions (~80%; P<0.05), which was co-localizated with BAFF (r=0.646; P<0.001), in the MZ. TACI and BCMA exhibited similar expression among the different zones of the GCs, and co-localization with BAFF was observed inside the follicle, mainly in the dark zone. The present results indicate that BAFF is implicated in the maintenance of GCs. BAFF-R overexpression in the MZ, co-localizated with BAFF, suggests that these proteins constitute the principal pathway for the maintenance of the naïve B-cell population. Furthermore, TACI and BCMA have a role in the GC, where processes of B-cell selection, proliferation and differentiation into immunoglobulin-secreting plasma cells occur.

Association of CD28 and CTLA4 haplotypes with susceptibility to primary Sjögren's syndrome in Mexican population.

BACKGROUND: Primary Sjögren's syndrome (pSS) is an autoimmune disease characterized by destruction of exocrine glands as a result of T and B cells infiltrated in glandular tissue. CD28 and CTLA-4 play a crucial role in T cell activation and inhibition. The aim of this study was to associate CD28 and CTLA4 haplotypes with susceptibility to pSS in patients from western Mexico. METHODS: Polymerase chain reaction and restriction fragment length polymorphism were performed to identify CD28 and CTLA4 genotypes in 111 patients with pSS and 138 control subjects (CS). Haplotype analysis was carried out by SHEsis program. Soluble serum levels of CD28 (sCD28) and CTLA-4 (sCTLA-4) were quantified by ELISA kit. RESULTS: The CD28 GC haplotype was associated with low risk to pSS (2.5-folds, P < 0.001). CTLA4 CAG and CGA were identified as genetic risk factor (P < 0.001;OR = 3.82[CI95%:2.022-7.296] and P < 0.001; OR = 11.38[CI95%:3.282-37.69] respectively). No difference in sCD28 and sCTLA-4 were found between patients and CS. However, pSS patients carriers of CD28 IVS3 + 17TC genotype showed high sCD28 (P = 0.039 vs TT carriers in CS). In regard to sCTLA-4, patient who carry CTLA4-319C>T, +49 A>G, and +6230 G>A, or their haplotypes did not show any difference. CONCLUSION: Our findings suggest that CD28 GC, CTLA4 CAG, and CGA haplotypes are associated with susceptibility to pSS in patients from western Mexico. It seems that genetic control of CD28 and CTLA4 as well as local immune response in glandular tissue may regulate the impact of the gene expression in pSS. It is necessary to confirm this hypothesis in an integrative study.