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Introduction. The serotoninergic system seems to be implicated in characteristic symptoms of borderline personality disorder (BPD) such as affective instability, impulsivity or suicide. Some studies suggest an association between serotonin transporter gene (5-HTT) polymorphisms and some BPD symptoms. Short allele (S) of the 5-HTTLPR polymorphism in the promoter region has been shown to be associated with impulsivity, aggressive behavior, anxiety and neuroticism. Of the variable number of tandem repeat (VNTR) polymorphism in intron 2, BPD patients showed higher frequencies of the allele with the 10 repeats. The aim of this study was to determine the association between 5-HTTLPR and VNTR polymorphism of 5-HTT and personality traits in borderline personality disorder. Method. A total of 65 BPD patients diagnosed by means of semi-structured interviews SCID-II and DIB-R were included. Two common polymorphisms of 5-HTT were genotyped: the 5-HTTLPR in the promoter region and VNTR in intron 2. Personality traits were assessed by the Zuckerman-Kuhlman Personality Questionnaire (ZKPQ). Results. Patients with L allele (L/S or L/L) in the 5-HTTLPR polymorphism showed lower scores on the subscale of liking parties and friends. Patients with the allele with 10 repeat of the VNTR polymorphism, showed lower scores in impulsivity, sensation seeking and in the subscale liking of parties and friends. Conclusions. The results suggest a significant association between the 5-HTT gene and some personality traits in BPD. This gene may play a role in the etiology of borderline personality disorder. [ABSTRACT FROM AUTHOR]

Objective: The PD-1 axis promotes protection against autoimmunity. Immune checkpoint (IC) molecules performance in anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV) remains unknown. This study aims to assess the IC pathway's role in the AAV's pathophysiology., Methods: We recruited 88 AAV from our centre as a discovery cohort (acute=42, remission=46) and 30 patients from another institution for external validation (acute=16, remission=14).Serum, urine and peripheral blood mononuclear cells (PBMCs) were collected. In vitro IC molecules production by lymphocytes was studied with and without MPO/PR3 antigen stimulus. Cell culture supernatant (SN) was obtained by centrifugation. PD-1, PD-L1 and PD-L2 concentrations were assessed in serum (s), urine (u) and SN of AAV and healthy controls (HC) using a multiplex assay. PD-1 and PD-L1's expression was analysed in six diagnostic kidney biopsies., Results: uPD-1 and uPD-L2's concentration was lower in AAV than HC (p<0.0001, p=0.0075). Acute patients exhibited lower uPD-L2 levels compared with those in remission (p=0.036). Similarly, PBMCs showed reduced PD-1 production than HC (stimulated group p=0.04, unstimulated p=0.0074). Furthermore, patients with inflammatory renal lesions had fewer PD-1-positive interstitial cells/staining intensity compared with those with sclerotic lesions. Contradictorily, sPD-1 and sPD-L1's concentration was higher in AAV than HC (p=0.007, p<0.0001) with acute patients exhibiting elevated sPD-1 levels compared with those in remission (p=0.0051). Serum and urine findings were confirmed in the validation cohort., Conclusions: Results in urine, SN and histology suggest IC pathway abolition during acute disease restored in remission and contribute to understand PD-1 axis's role in AAV proposing it as a new biomarker of disease activity., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Severe ischemia-reperfusion injury (IRI) causes acute and chronic kidney allograft damage. As therapeutic interventions to reduce damage are limited yet, research on how to promote kidney repair has gained significant interest. To address this question, we performed genome-wide transcriptome and epigenome profiling in progenitor cells isolated from the urine of deceased (severe IRI) and living (mild IRI) donor human kidney transplants and identified LIM homeobox-1 (LHX1) as an epigenetically regulated gene whose expression depends on the IRI severity. Using a mouse model of IRI, we observed a relationship between IRI severity, LHX1 promoter hypermethylation, and LHX1 gene expression. Using functional studies, we confirmed that LHX1 expression is involved in the proliferation of epithelial tubular cells and podocyte differentiation from kidney progenitor cells. Our results provide evidence that severe IRI may reduce intrinsic mechanisms of kidney repair through epigenetic signaling., Competing Interests: Declaration of competing interest The authors of this manuscript have no conflicts of interest to disclose as described by the American Journal of Transplantation., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background : Sinonasal exophytic papillomas (SNEP) are benign tumours arising from nasal mucosa. Human papillomavirus (HPV) infection seems to be related to the aetiology of a fraction of SNEP cases. SNEP presentation can be focal (FSNEP) or diffuse (DSNEP), but factors related to focal or diffuse presentation have not yet been well ascertained. This study aimed to analyse clinical, histological, and HPV-related differences between FSNEP and DSNEP. Methods : A retrospective cohort of 18 patients with SNEP from our centre were evaluated. Demographic, clinical and follow-up data were collected. All samples were subject to histopathological evaluation, DNA quality control, HPV-DNA detection, and viral load assessment. Univariate analyses were performed to evaluate differences between FSNEP and DSNEP. Results : Twelve SNEP patients were included in the final analysis. Seven patients had a diffuse nasal presentation, being younger than patients affected with FSNEP (42.7 years vs. 65.2 years, p = 0.019). The nasal septum was significantly more affected in DSNEP than in FSNEP (85.7% vs. 20%, p = 0.029). HPV-DNA was detected more frequently (100%) in DSNEP (HPV11 in six cases, HPV6 in one case) than in FSNEP (40%, p = 0.045, HPV6 in two cases). The median viral load among HPV6-positive samples was 626.8 virus/cell for FSNEP and 80.2 for DSNEP, and among HPV11-positive samples was 1673.7 for DSNEP. Recurrences were more frequent in the diffuse than in the focal group (85.7% vs. 20%, p = 0.029). Conclusions : The diffuse presentation of SNEP seems to be related to younger patients, nasal septum involvement, HPV infection, mostly HPV11, and a higher risk of recurrence.

Background: Acute interstitial nephritis (AIN) related to immune checkpoint inhibitors (ICI-AIN) has a not completely understood pathophysiology. Our objectives were to analyze possible biomarkers for the differentiation between acute tubular necrosis (ATN) and AIN, especially in cancer patients, and to study the participation of the immune checkpoint pathway in ICI-AIN., Methods: We performed an observational study. We recruited patients with incident diagnosis of ICI-AIN ( n  = 19). We measured soluble PD-1 (sPD-1), sPD-L1, and sPD-L2 in serum and urine at diagnosis and compared to it patients with non-ICI-related AIN (non-ICI-AIN) ( n  = 18) and ATN ( n  = 21). The findings were validated in an independent cohort from another institution ( n  = 30). Also, we performed PD-L1 and PD-L2 immunostaining of kidney biopsies from patients with ICI-AIN and compared to patients with non-ICI-AIN., Results: Urinary sPD-1 (usPD-1) was higher in patients with AIN compared to ATN ( P  = .03). Patients with AIN also showed higher serum sPD-1 (ssPD-1) than patients with ATN ( P  = .021). In cancer patients, usPD-1 <129.3 pg/ml had a 71.43% sensitivity and 94.44% specificity to differentiate ATN from ICI-AIN, with a likelihood ratio of 12.86. In the external validation cohort, the same cutoff showed a sensitivity of 80%. In kidney biopsies, patients with ICI-AIN showed higher density of PD-L1 positive tubules than patients with non-ICI-AIN ( P  = .02). The proportion of patients having >2.64/mm 2 PD-L2 positive tubules was higher among patients with ICI-AIN compared to non-ICI-AIN ( P  = .034). There was a positive correlation ( P  = .009, r  = 0.72) between usPD-1 and the number of PD-L1 positive tubules., Conclusions: UsPD-1 and ssPD-1 are higher in AIN than ATN. Moreover, there was a strong correlation between usPD-1 and renal tubular PD-L1 expression. Our findings suggest a role of usPD-1 as non-invasive biomarker to differentiate ICI-AIN from ATN, especially in cancer patients, which has been confirmed in an external validation cohort., Competing Interests: None declared., (© The Author(s) 2024. Published by Oxford University Press on behalf of the ERA.)

Introduction: Immune checkpoint inhibitors (ICIs) induce acute interstitial nephritis (AIN) in 2-5% of patients, with a clearly higher incidence when they are combined with platinum derivatives. Unfortunately, suitable disease models and non-invasive biomarkers are lacking. To fill this gap in our understanding, we investigated the renal effects of cisplatin and anti-PD-L1 antibodies in mice, assessing PD-1 renal expression and cytokine levels in mice with AIN, and then we compared these findings with those in AIN-diagnosed cancer patients., Methods: Twenty C57BL6J mice received 200 µg of anti-PD-L1 antibody and 5 mg/kg cisplatin intraperitoneally and were compared with those receiving cisplatin (n = 6), anti-PD-L1 (n = 7), or saline (n = 6). After 7 days, the mice were euthanized. Serum and urinary concentrations of TNFα, CXCL10, IL-6, and MCP-1 were measured by Luminex. The kidney sections were stained to determine PD-1 tissue expression. Thirty-nine cancer patients with AKI were enrolled (AIN n = 33, acute tubular necrosis (ATN) n = 6), urine MCP-1 (uMCP-1) was measured, and kidney sections were stained to assess PD-1 expression., Results: Cisplatin and anti PD-L1 treatment led to 40% AIN development (p = 0.03) in mice, accompanied by elevated serum creatinine and uMCP1. AIN-diagnosed cancer patients also had higher uMCP1 levels than ATN-diagnosed patients, confirming our previous findings. Mice with AIN exhibited interstitial PD-1 staining and stronger glomerular PD-1 expression, especially with combination treatment. Conversely, human AIN patients only showed interstitial PD-1 positivity., Conclusions: Only mice receiving cisplatin and anti-PDL1 concomitantly developed AIN, accompanied with a more severe kidney injury. AIN induced by this drug combination was linked to elevated uMCP1, consistently with human AIN, suggesting that uMCP1 can be potentially used as an AIN biomarker., (© 2024. The Author(s).)

Introduction: There is a need to implement routine perinatal mental health screening in Spain. Therefore, it is necessary to systematise the detection of depressive and anxious symptoms in pregnancy and postpartum using the same instrument. The Edinburgh Postnatal Stress Depression Scale (EPDS) is frequently used as a rapid, effective and cross-culturally validated screening tool for perinatal depression. In several countries, an Anxiety subscale, the EPDS-A, was identified within the EPDS. Although the factorial structure of the EPDS has been investigated in Spanish population, the EPDS-A has not yet been validated. This study aimed to validate the EPDS-A as a measure of perinatal anxiety in Spanish population., Methods: 161 women were evaluated with the EPDS and the State-Trait Anxiety Inventory (STAI) during pregnancy and postpartum. Confirmatory factor analysis (CFA) was used to confirm the trifactorial structure of the EPDS, comprising the dimensions of Depression, Anhedonia and Anxiety. Likewise, the invariance of the trifactorial model between pregnancy and postpartum was tested. Finally, the correlations between the EPDS-A and the STAI subscales (State Anxiety and Trait Anxiety) were calculated., Results: The Exploratory factor analysis (EFA) driven three-factor structure of the EPDS, consisting of an Anhedonia factor (Items 1, 2, and 10), an Anxiety factor (Items 3, 4, 5, and 6) and a Depression factor (Items 7, 8, and 9), was the best measurement model for the current data compared to the alternative model tested [χ 2  = 34.592, df  = 32, p  = 0.34; χ 2 / df  = 1.08; RMSEA = 0.023, 90% Confidence Interval [CI] [0.000, 0.064], CFI = 0.996, GFI = 0.960]. The model's invariance between pregnant and postpartum women was confirmed. The existence of an Anxiety subscale within the EPDS was also confirmed. The scores obtained with the EPDS-A correlated moderately with scores on both subscales of the STAI during pregnancy and after delivery. Using the STAI as a criterion and prioritising the instrument's sensitivity, a cut-off point of 4 points was established for the EPDS-A., Conclusion: Our results confirm the trifactorial structure of the EPDS in Spanish population. The Anxiety subscale was validated for routine perinatal mental health screening., 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 Gomà, Gordo, Cozodoy, Iriarte, Prims, Ferrer, Sánchez, Llairó and Arias-Pujol.)

Maternal representations play a key role in intrapsychic conflicts relating to accession to parenthood and in the formation of the mother-baby bond. Around the birth of the child, the shadows of past objects are cast on the baby and the parent's self-image. Mother-baby psychoanalytic psychotherapy helps us to understand internal conflicts that tend to interfere with the mother's representations of her child or of herself as a mother, as well as aiming to reduce the risk of difficulties for the child. Through a clinical case, this article explores the development of maternal representations in a course of parenthood-centred psychotherapy that begins during pregnancy and ends 11 months after the baby's birth. The psychic change carried out by the mother frees the mother-baby bond from the projections of the past. Excerpts from clinical sessions illustrate mother-baby interactions during the session, the projection of the mother's internal objects on to the baby, and the elaboration and reintrojection of the mother's internal conflicts. Changes in the mother's representations were measured both qualitatively and quantitatively using the 'R' interview, which allows various dimensions of these representations to be measured on a Likert scale.

The treatment of head and neck and salivary gland tumours is complicated and is constantly evolving. Prognostic and predictive indicators of response to treatment are enormously valuable for designing individualized therapies, which justifies their research and validation. Some biomarkers, such as p16, Epstein-Barr virus, PD-L1, androgen receptors and HER-2, are already used routinely in clinical practice. These biomarkers, along with other markers that are currently under development, and the massively parallel sequencing of genes, ensure future advances in the treatment of these neoplasms. In this consensus, a group of experts in the diagnosis and treatment of tumours of the head and neck and salivary glands were selected by the Spanish Society of Pathology (Sociedad Española de Anatomía Patológica - SEAP) and the Spanish Society of Medical Oncology (Sociedad Española de Oncología Médica - SEOM) to evaluate the currently available information and propose a series of recommendations to optimize the determination and daily clinical use of biomarkers., (Copyright © 2022. Publicado por Elsevier España, S.L.U.)

The treatment of head and neck and salivary gland tumours is complicated and evolves constantly. Prognostic and predictive indicators of response to treatment are enormously valuable for designing individualized therapies, which justifies their research and validation. Some biomarkers, such as p16, Epstein-Barr virus, PD-L1, androgen receptors and HER-2, are already used routinely in clinical practice. These biomarkers, along with other markers that are currently under development, and the massively parallel sequencing of genes, ensure future advances in the treatment of these neoplasms. In this consensus, a group of experts in the diagnosis and treatment of tumours of the head and neck and salivary glands were selected by the Spanish Society of Pathology (Sociedad Española de Anatomía Patológica-SEAP) and the Spanish Society of Medical Oncology (Sociedad Española de Oncología Médica-SEOM) to evaluate the currently available information and propose a series of recommendations to optimize the determination and daily clinical use of biomarkers., (© 2022. The Author(s).)

Systemic lupus erythematosus is a complex autoimmune disorder mostly mediated by B-cells in which costimulatory signals are involved. This immune dysregulation can cause tissue damage and inflammation of the kidney, resulting in lupus nephritis and chronic renal failure. Given the previous experience reported with CTLA4-Ig as well as recent understanding of the PD-1 pathway in this setting, our group was encouraged to evaluate, in the NZBWF1 model, a human fusion recombinant protein (Hybri) with two domains: CTLA4, blocking the CD28-CD80 costimulatory pathway, and PD-L2, exacerbating the PD-1-PD-L2 coinhibitory pathway. After achieving good results in this model, we decided to validate the therapeutic effect of Hybri in the more severe MRL/lpr model of lupus nephritis. The intraperitoneal administration of Hybri prevented the progression of proteinuria and anti-dsDNA antibodies to levels like those of cyclophosphamide and reduced the histological score, infiltration of B-cells, T-cells, and macrophages and immune deposition in both lupus-prone models. Additionally, Hybri treatment produced changes in both inflammatory-related circulating cytokines and kidney gene expression. To summarize, both in vivo studies revealed that the Hybri effect on costimulatory-coinhibitory pathways may effectively mitigate lupus nephritis, with potential for use as a maintenance therapy.

Achieving fast immunosuppression blood exposure after kidney transplantation is key to abrogating both preformed and de novo anti-donor humoral and cellular alloresponses. However, while tacrolimus (TAC) is the cornerstone immunosuppressant inhibiting adaptive alloimmunity, its blood exposure is directly impacted by different single-nucleotide polymorphisms (SNPs) in CYP3A TAC-metabolizing enzymes. Here, we investigated how functional TAC-CYP3A genetic variants ( CYP3A4*22 / CYP3A5*3 ) influence the main baseline clinical and immunological risk factors of biopsy-proven acute rejection (BPAR) by means of preformed donor-specific antibodies (DSAs) and donor-specific alloreactive T cells (DSTs) in a large European cohort of 447 kidney transplants receiving TAC-based immunosuppression. A total of 70 (15.7%) patients developed BPAR. Preformed DSAs and DSTs were observed in 12 (2.7%) and 227 (50.8%) patients, respectively. According to the different CYP3A4*22 and CYP3A5*3 functional allele variants, we found 4 differential new clusters impacting fasting TAC exposure after transplantation; 7 (1.6%) were classified as high metabolizers 1 (HM1), 71 (15.9%) as HM2, 324 (72.5%) as intermediate (IM), and 45 (10.1%) as poor metabolizers (PM1). HM1/2 showed significantly lower TAC trough levels and higher dose requirements than IM and PM (p < 0.001) and more frequently showed TAC underexposure (<5 ng/ml). Multivariate Cox regression analyses revealed that CYP3A HM1 and IM pharmacogenetic phenotypes (hazard ratio (HR) 12.566, 95% CI 1.99-79.36, p = 0.007, and HR 4.532, 95% CI 1.10-18.60, p = 0.036, respectively), preformed DSTs (HR 3.482, 95% CI 1.99-6.08, p < 0.001), DSAs (HR 4.421, 95% CI 1.63-11.98, p = 0.003), and delayed graft function (DGF) (HR 2.023, 95% CI 1.22-3.36, p = 0.006) independently predicted BPAR. Notably, a significant interaction between T-cell depletion and TAC underexposure was observed, showing a reduction of the BPAR risk (HR 0.264, 95% CI 0.08-0.92, p = 0.037). Such variables except for DSAs displayed a higher predictive risk for the development of T cell-mediated rejection (TCMR). Refinement of pretransplant monitoring by incorporating TAC CYP3A SNPs with preformed DSAs as well as DSTs may improve current rejection-risk stratification and help induction treatment decision-making., 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. The reviewer L.R has declared a shared affiliation with the author T.J to the handling editor at the time of review., (Copyright © 2022 Crespo, Vidal-Alabró, Jouve, Fontova, Stein, Mocka, Meneghini, Sefrin, Hruba, Gomà, Torija, Donadeu, Favà, Cruzado, Melilli, Moreso, Viklicky, Bemelman, Reinke, Grinyó, Lloberas and Bestard.)

Human papillomavirus (HPV)-related oropharyngeal squamous cell carcinomas (OPSCCs) represent a distinct clinical entity compared with HPV-negative tumors with particular regard to treatment response and survival outcome. The aim of this study was to assess the AmpFire Multiplex HR-HPV tests, for the detection and genotyping of 15 high-risk (HR) HPV types in formalin-fixed, paraffin-embedded (FFPE) samples and identify HPV-driven OPSCC. DNA from 160 OPSCC FFPE specimens plus 23 samples from other head and neck primary sites was tested. Results were compared with those obtained using Linear Array HPV-DNA Genotyping Test. Linear Array and AmpFire Multiplex HR-HPV tests showed, for all samples and specifically for OPSCCs, an overall concordance agreement of 98.9% and 99.4% and a Cohen κ coefficient of 0.972 and 0.984, respectively. A concordance of 100% for HPV16 and HPV18 was observed. The overall agreement between p16 INK4a overexpression and HPV detection by the AmpFire Multiplex HR-HPV assay in 145 OPSCC samples was 93.8%, with a Cohen κ coefficient of 0.848. The AmpFire HPV Tests are simple assays for detection and genotyping of HPV-DNA in OPSCC FFPE samples and can be easily implemented in the clinical practice setting for HPV-DNA detection., (Copyright © 2022 Association for Molecular Pathology and American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.)

mRNA-based vaccines have dramatically shifted the course of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic. IgA nephropathy (IgAN) flare is the most reported renal adverse effect after the administration of these vaccines. Unraveling the mechanistic pathways leading to these flares is necessary to confirm a causal association. Herein, we report 2 cases of IgAN flare after SARS-CoV-2 vaccination in patients previously diagnosed with IgAN. We describe and compare the clinical and analytical features of the disease at the time of the diagnostic with the post-vaccine flare. In addition, we obtained serum and urine of these patients at the moment of the flare and determined the levels of IL-2, TNF-α, and IFNγ using a multiplex bead-based assay. As diseased controls, we included n = 13 patients diagnosed with IgAN who had available serum and urine samples at the moment of the diagnostic stored in our biobank. We also included 6 healthy controls. Compared to the first episode, postvaccination flares were more severe in terms of peak serum creatinine, albuminuria, and urinary erythrocyte count. The histological lesions found at the biopsy performed during the post-vaccine flare were similar to those found at the diagnostic. One of the patients who suffered a post-vaccine flare showed increased serum IL-2 and TNFα compared to the IgAN-diseased controls and the healthy controls. In conclusion, although several cases of post-vaccine IgAN flares have been reported, there are no mechanistic studies on the occurrence of these flares. We here suggest that hyperactivation of the Th1 pathway may be involved, but larger studies with more refined methods for numerical and functional Th1 lymphocytes evaluation are required., (© 2022 S. Karger AG, Basel.)

Aim: To determine the prevalence of anxiety-depressive symptomatology and associated risk factors in a population of pregnant women in the low-income neighborhood of Roquetes (Barcelona, Spain)., Design: Quasi-experimental, cross-sectional study., Location: The study was carried out at the Primary Care Center, Roquetes Canteres, Barcelona., Participants: Between 2015 and 2017, all pregnant women who visited the Sexual and Reproductive Care Team in Primary Care (ASSIR) or their Family Physician (FP) were invited to take part in a study if they met the following criteria: (a) over 18 years old (b) able to understand in any of the 4 study languages. Of a total of 239 gestating women, 19 declined to participate, 14 moved away from the area and 16 underwent voluntary termination of pregnancy, leaving a sample of 190 subjects., Material and Methods: The Edinburgh Postnatal Depression Scale (EPDS) was used to detect depressive symptomatology, the State-Trait Anxiety Inventory (STAI) was used to assess anxiety, and a sociodemographic data questionnaire was administered. Once all descriptive demographic data from the whole sample was analyzed, baseline clinical and demographic characteristics were compared using the independent t-test for continuous variables and the chi-squared analysis for categorical variables., Results: The t-test showed that 48% of pregnant women presented an at-risk degree of anxiety-depressive symptomatology, double that found in the general population. Applying a chi-squared test to the at-risk and non-risk groups revealed associated prenatal risk factors including: having a history of violence; living in a rented room, mistreatment in infancy and mental health issues. The ROC curves analysis obtained a cutoff point score of 4 Accumulated Associated Factors (AAF) (AUC 0.765, p  < .001, 57% sensitivity and 79% specificity)., Conclusions: Our study shows that rates of anxiety-depressive symptomatology in a population with considerable socio-economic deprivation can more than double. AAF in the population at risk of anxiety and depression were detected, highlighting the need to allocate resources to identification and prevention during pregnancy. This requires the involvement of a multidisciplinary, professional team with a biopsychosocial perspective.

Systemic lupus erythematosus is a highly complex and heterogeneous autoimmune disease mostly mediated by B cells. It is characterized by circulating self-reactive antibodies that deposit and form immune complexes in kidney, leading to irreparable tissue damage and resulting in lupus nephritis. In a New Zealand Black X New Zealand White F1 mouse model, we tested two different small interfering RNA (siRNA) silencing treatments against interferon regulatory factor 5 (IRF5) and B cell-activating factor (BLYSS) expression and their combination in a second set of animals. The administration of these two siRNAs separately prevented the progression of proteinuria and albuminuria at similar levels to that in cyclophosphamide animals. These treatments effectively resulted in a reduction of serum anti-double-stranded DNA (dsDNA) antibodies and histopathological renal score compared with non-treated group. Treated groups showed macrophage, T cell, and B cell infiltrate reduction in renal tissue. Moreover, kidney gene expression analysis revealed that siRNA treatments modulated very few pathways in contrast to cyclophosphamide, despite showing similar therapeutic effects. Additionally, the combined therapy tested in a second set of animals, in which the disease appeared more virulent, exhibited better results than monotherapies in the disease progression, delaying the disease onset and ameliorating the disease outcome. Herein, we provide the potential therapeutic effect of both selective IRF5 and BLYSS silencing as an effective and potential treatment, particularly in early phases of the disease., Competing Interests: The authors declare no competing interests., (© 2021 The Authors.)