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Introduction: Immunoglobulin A (IgA) is the main antibody isotype in body fluids such as tears, intestinal mucous, colostrum, and saliva. There are two subtypes of IgA in humans: IgA1, mainly present in blood and mucosal sites, and IgA2, preferentially expressed in mucosal sites like the colon. In clinical practice, immunoglobulins are typically measured in venous or capillary blood; however, alternative samples, including saliva, are now being considered, given their non-invasive and easy collection nature. Several autoimmune diseases have been related to diverse abnormalities in oral mucosal immunity, such as rheumatoid arthritis, Sjogren's syndrome, and systemic lupus erythematosus (SLE)., Methods: We decided to evaluate the levels of both IgA subtypes in the saliva of SLE patients. A light chain capture-based ELISA measured specific IgA1 and IgA2 levels in a cohort of SLE patients compared with age and gender-matched healthy volunteers., Results: Surprisingly, our results indicated that in the saliva of SLE patients, total IgA and IgA1 subtype were significantly elevated; we also found that salivary IgA levels, particularly IgA2, positively correlate with anti-dsDNA IgG antibody titers. Strikingly, we also detected the presence of salivary anti-nucleosome IgA antibodies in SLE patients, a feature not previously reported elsewhere., Conclusions: According to our results and upon necessary validation, IgA characterization in saliva could represent a potentially helpful tool in the clinical care of SLE patients with the advantage of being a more straightforward, faster, and safer method than manipulating blood samples., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Romero-Ramírez, Sosa-Hernández, Cervantes-Díaz, Carrillo-Vázquez, Meza-Sánchez, Núñez-Álvarez, Torres-Ruiz, Gómez-Martín and Maravillas-Montero.)

Lupus nephritis (LN) is one of the most common manifestations of systemic lupus erythematosus (SLE), characterized by abnormal B cell activation and differentiation to memory or plasma effector cells. However, the role of these cells in the pathogenesis of LN is not fully understood, as well as the effect of induction therapy on B cell subsets, possibly associated with this manifestation, like aged-associated B cells (ABCs). Consequently, we analyzed the molecules defining the ABCs subpopulation (CD11c, T-bet, and CD21) through flow cytometry of blood samples from patients with lupus presenting or not LN, following up a small sub-cohort after six months of induction therapy. The frequency of ABCs resulted higher in LN patients compared to healthy subjects. Unexpectedly, we identified a robust reduction of a CD21 hi subset that was almost specific to LN patients. Moreover, several clinical and laboratory lupus features showed strong and significant correlations with this undefined B cell subpopulation. Finally, it was observed that the induction therapy affected not only the frequencies of ABCs and CD21 hi subsets but also the phenotype of the CD21 hi subset that expressed a higher density of CXCR5. Collectively, our results suggest that ABCs, and more importantly the CD21 hi subset, may work to assess therapeutic response since the reduced frequency of CD21 hi cells could be associated with the onset of LN., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Sosa-Hernández, Romero-Ramírez, Cervantes-Díaz, Carrillo-Vázquez, Navarro-Hernandez, Whittall-García, Absalón-Aguilar, Vargas-Castro, Reyes-Huerta, Juárez-Vega, Meza-Sánchez, Ortiz-Navarrete, Torres-Ruiz, Mejía-Domínguez, Gómez-Martín and Maravillas-Montero.)

Abstract: Systemic lupus erythematosus (SLE) is a chronic inflammatory autoimmune disease with a wide range of clinical presentations. Lupus nephritis (LN) is a frequent complication of SLE, representing a significant cause of morbidity and mortality in these patients. In addition, LN diagnosis remains suboptimal in most clinical contexts. The current gold standard for LN clinical diagnosis is a renal biopsy. Still, the invasiveness of this technique is an obstacle to the early detection of renal involvement and further monitoring of treatment results. Consequently, there are different areas for improvement in the field of LN, such as the search for novel non-invasive clinical biomarkers with an adequate correlation between clinical manifestations and actual histological damage. Although urine component-related studies are promising, the more robust blood/serum biomarkers may still be helpful in developing point-of-care systems that can be adapted to most clinical scenarios. Therefore, this brief review aims to highlight and summarize some of the most recently reported non-classical serum/blood potential LN biomarkers. (Rev Invest Clin. 2022;74(5):227-31)., (Copyright: © 2022 Permanyer.)

Background: Neutrophil extracellular traps (NETs) from patients with systemic lupus erythematosus (SLE) are characterized by lower ubiquitylation and myeloperoxidase (MPO) as a substrate. The structural and functional effect of such modification and if there are additional post-translational modifications (PTMs) are unknown., Methods: To assess the expression and functional role of PTMs in NETs of patients with SLE; reactivation, proliferation and cytokine production was evaluated by flow cytometry using co-cultures with dendritic cells (DC) and CD4 + from SLE patients and healthy controls. The impact of ubiquitylation on MPO was assessed by molecular dynamics. The expression of ISG15 in NETs was evaluated by immunofluorescence and Western Blot., Results: Fifteen patients with SLE and ten healthy controls were included. In the co-cultures of CD4 + lymphocytes with DC stimulated with ubiquitylated MPO or recombinant MPO, a higher expression of IFNγ and IL-17A was found in CD4 + from SLE patients (p < 0.05). Furthermore, with DC stimulated with ubiquitylated MPO a trend towards increased expression of CD25 and Ki67 was found in lupus CD4 + lymphocytes, while the opposite was documented in controls (p < 0.05). Through molecular dynamics we found the K129-K488-K505 residues of MPO as susceptible to ubiquitylation. Ubiquitylation affects the hydration status of the HEME group depending on the residue to which it is conjugated. R239 was found near by the HEME group when the ubiquitin was in K488-K505. In addition, we found greater expression of ISG15 in the SLE NETs vs controls (p < 0.05), colocalization with H2B (r = 0.81) only in SLE samples and increased production of IFNγ in PBMCs stimulated with lupus NETs compared to healthy controls NETs., Conclusion: The ubiquitylated MPO has a differential effect on the induction of reactivation of CD4 + lymphocytes in patients with SLE, which may be related to structural changes by ubiquitylation at the catalytic site of MPO. Besides a lower ubiquitylation pattern, NETs of patients with SLE are characterized by the expression of ISG15, and the induction of IFNγ by Th1 cells.

We have identified Tspan33 as a gene encoding a transmembrane protein exhibiting a restricted expression pattern including expression in activated B cells. TSPAN33 is a member of the tetraspanin family. TSPAN33 is not expressed in resting B cells, but is strongly induced in primary human B cells following activation. Human 2E2 cells, a Burkitt's lymphoma-derived B cell model of activation and differentiation, also upregulate TSPAN33 upon activation. TSPAN33 is expressed in several lymphomas including Hodgkin's and Diffuse large B cell lymphoma. TSPAN33 is also expressed in some autoimmune diseases where B cells participate in the pathology, including rheumatoid arthritis patients, systemic lupus erythematosus (SLE), and in spleen B cells from MRL/Fas(lpr/lpr) mice (a mouse model of SLE). We conclude that TSPAN33 may be used as a diagnostic biomarker or as a target for therapeutic antibodies for treatment of certain B cell lymphomas or autoimmune diseases., (© 2013.)