Sjögren's syndrome and pregnancy: a Portuguese case-control study.

Introduction: Pregnancy in patients with autoimmune disorders is associated with an increased risk of adverse outcomes. Sjögren's syndrome (SS) is one of the most common among autoimmune diseases. Presently data regarding the impact of SS on obstetric outcomes are scarce and inconclusive. This study aims to evaluate the impact of SS on maternal-fetal and neonatal outcomes compared with pregnancy outcomes in the general population. Material and methods: A retrospective case-control study included 26 pregnancies in SS patients and a healthy control group (CG), followed in a Portuguese tertiary center, between 2015 and 2020. Baseline maternal data were collected, and maternal-fetal and neonatal outcomes were evaluated. Statistical analysis used SPSS 25.0, and a p-value of 0.05 was considered statistically significant. Results: All pregnancies occurred after the diagnosis of SS, with a mean exposure time between diagnosis and pregnancy of 4.92 ±2.78 years. In the SS group, the incidence of ANA, anti-Ro/SSA, and anti-La/SSB antibodies positivity was 80.8%, 61.5%, and 46.2%, respectively. Hydroxychloroquine (HCQ) was used in 57.7%.Miscarriage was significantly higher in the SS group (19.2% vs. 1.8%, p < 0.01). There was a higher prevalence of fetal growth restriction (OR 11.16, 95% CI: 0.96-129.26). Preterm delivery (9.5% vs. 5.6%, p = 0.503) and mean birth weight (2998.16 g vs. 3155.79 g, p = 0.178) did not differ significantly between the groups. In the SS group, admission to the neonatal intensive care unit (NICU) rate was increased (OR 71.67, 95% CI: 3.78-1357.16). Three pregnancies were complicated by congenital heart block (CHB) (14.3% vs. 0%, p = 0.015). In all cases, the diagnosis was performed during second trimester of pregnancy, and betamethasone was administered. Conclusions: Women with SS had a significantly higher incidence of miscarriage, admission to NICU, and CHB than controls. Congenital heart block was the most critical condition that affects the offspring of mothers with SS. Successful pregnancy in the study group was possible with prenatal monitoring and a multidisciplinary approach.

Systemic lupus erythematosus and pregnancy: A retrospective single-center study of 215 pregnancies from Portugal.

OBJECTIVE: Systemic lupus erythematosus (SLE) is a life-threatening disorder that affects women at reproductive age. We evaluate the clinical impact of pregnancy in a cohort of Portuguese SLE patients and the risk factors associated with maternal and fetal adverse outcomes. METHODS: A retrospective observational study that included all pregnant women with SLE managed at a Portuguese tertiary hospital, between January 1993 and December 2019. Baseline maternal information was collected, and maternal-fetal and neonatal outcomes were evaluated. Disease activity before and during pregnancy was assessed. RESULTS: We included 215 pregnancies from 143 patients. Lupus nephritis was present in 20.0% and antiphospholipid syndrome (APS) in 21.9% of the cases. Preconception consultation was performed in 86.9% of the pregnancies, and 92.5% of the patients had no or low disease activity at conception. During gestation, 79.6% of the patients were under treatment, and hydroxychloroquine (HCQ) was the most commonly used drug (63.7%). Low-dose acetylsalicylic acid (ASA) was prescribed at conception in 87.9% of the patients. The live birth rate was 84.2%. An adverse pregnancy outcome (APO) occurred in 41.4% of the pregnancies. A miscarriage rate of 15.3% and a preterm delivery rate of 15.4% were found. Preeclampsia and fetal growth restriction complicated 13.1% and 14.0% of the gestations, respectively. Neonatal lupus occurred in 7.1% of the newborns, and there were 2 cases of congenital heart block. Significant risk factors for the development of AOP were disease activity at conception, lupus flare, hypocomplementemia, positivity for lupus anticoagulant, and APS. The use of ASA was significantly associated with a reduced incidence of miscarriage. An SLE flare was diagnosed in 16.3% of the cases. We identified as risk factors for lupus flares the presence of active disease at conception, a previous history of lupus nephritis, and the use of chronic medication. HCQ use during pregnancy was associated with a significant reduction of flare incidence during pregnancy and postpartum. CONCLUSIONS: Pregnancy in an SLE patient is associated with an increased incidence of adverse obstetric outcomes. Good disease control before pregnancy and adequate treatment, especially with HCQ, is crucial to achieving the best obstetric results.

Behçet's Disease and Pregnancy: A Retrospective Case-control Study.

Background: Behçet's disease (BD) is a rare chronic multisystemic vasculitis of unknown etiology. It is usually diagnosed between the 2nd and 4th decades of life, so its association with pregnancy is not unusual. This study aims to characterize the evolution of pregnancy in a group of pregnant women with BD and the impact of this pathology in embryo-fetal morbidity. Methods: A retrospective case-control study included 49 pregnancies in women suffering from BD, followed in our institution. Pregnancy outcomes were compared with a control group of healthy pregnant women. Two controls per case were randomly selected. Statistical analysis used SPSS 25.0, and a p-value of 0.05 was considered statistically significant. Results: Forty-nine pregnancies were included in 27 patients with BD. BD exacerbation occurred in 32.6% of the pregnancies. There were no significant statistical differences between the two groups regarding the rate of preterm delivery, gestational diabetes, and preeclampsia (p>0.05). In the BD group, we found a higher rate of miscarriage (24.5%) and fetal growth restriction (FGR, 13.3%, p<0.05). In the study group, 13 (32.5%) of the pregnant patients did not need treatment. The cesarean rate was significantly higher in the BD group (43.2% vs 20.4% in the control group, p<0.05), and there were no significant differences in median gestational age at the time of delivery (p>0.05). The birth weight of newborns did not differ significantly between the groups. There was no association of BD with maternal morbidity and neonatal complications. Conclusion: In this study, the majority of pregnant with BD did not present clinical exacerbation of their pathology. However, BD may have an adverse influence on pregnancy outcomes. FGR and miscarriage rates were significantly higher in the study group.

Eosinophilic fasciitis after parasite infection.

Eosinophilic fasciitis is a systemic inflammatory disease characterized by symmetrical swelling and skin induration of the distal portions of the arms and/or legs, evolving into a scleroderma-like appearance, accompanied by peripheral blood eosinophilia. It is a rare disease with a poorly understood etiology. Corticosteroid treatment remains the standard therapy, either taken alone or in association with an immunosuppressive drug. This paper presents a case of a male patient with palpebral edema and marked eosinophilia, diagnosed with intestinal parasitic infection in October 2006. He was treated with an antiparasitic drug, but both the swelling and the analytical changes remained. This was followed by a skin and muscle biopsy, which turned out to be compatible with eosinophilic fasciitis. There was progressive worsening of the clinical state, with stiffness of the abdominal wall and elevated inflammatory parameters, and the patient was referred to the Immunology Department, medicated with corticosteroids and methotrexate. Over the years there were therapeutic adjustments and other causes were excluded. Currently the patient continues to be monitored, and there is no evidence of active disease. The case described in this article is interesting because of the diagnosis of eosinophilic fasciitis probably associated/coexisting with a parasite infection. This case report differs from others in that there is an uncommon cause associated with the onset of the disease, instead of the common causes such as trauma, medication, non-parasitic infections or cancer.

Small Bowel Villous Atrophy in a Young Patient: A Challenging Diagnosis.

Common variable immunodeficiency enteropathy is a sprue-like disease, which may manifest as a severe malabsorption syndrome with nutritional deficits and cachexia. The authors report a case of a 33-year-old Afghan man, who presented to the emergency department due to chronic watery diarrhea and severe malnourishment. He had been previously misdiagnosed with celiac disease in his early adulthood; however, this was based on inconclusive findings. After a thorough diagnostic workup, the final diagnosis of common variable immunodeficiency enteropathy with symptomatic norovirus infection of the gut was obtained during his prolonged hospitalization. A slow but progressive improvement was observed with immunoglobulin replacement therapy, corticotherapy, and ribavirin treatment. This is a noteworthy case of a rare malabsorption disorder, and it reviews important aspects concerning the differential diagnosis of small bowel villous atrophy of unknown etiology, as well as gastrointestinal manifestations of common variable immunodeficiency disorder.

A Enteropatia associada à Imunodeficiência Comum Variável é uma entidade com características clínicas e endoscópicas semelhantes à doença celíaca. Por vezes apresenta-se como um síndrome de malabsorção, levando a défices nutricionais e caquexia severa. Os autores relatam o caso de um homem de 33 anos de idade de naturalidade afegã, que recorreu ao serviço de urgência por um quadro de diarreia aquosa crónica e desnutrição severa. O doente teria sido diagnosticado erroneamente com doença celíaca no início da vida adulta, com bases em dados clínicos inconclusivos. Após um estudo exaustivo durante um internamento prolongado, o doente foi diagnosticado com uma Enteropatia associada à Imunodeficiência Comum Variável com sobreinfeção por Norovirus. Foi observada uma melhoria lenta e progressiva com instituição de terapêutica substitutiva com imunoglobulina, corticoterapia e ribavirina. Este caso retrata uma causa rara de malabsorção, abordando pontos essenciais no diagnóstico diferencial da atrofia vilositária do intestinal delgado, bem como das manifestações gastrointestinais da Imunodeficiência Comum Variável.

Update on Femtosecond Laser-Assisted Cataract Surgery: A Review.

The advent of femtosecond lasers has resulted in a new standard in cataract surgery, intended to overmatch the paradigm of conventional phacoemulsification. Femtosecond laser-assisted cataract surgery (FLACS) enables a higher level of reproducibility, precision, accuracy, and customization when performing several steps of cataract (or lens) surgery. Capsulotomy, corneal incisions, lens fragmentation, and arcuate incisions are the main procedures performed using FLACS. As the demand for better refractive outcomes and spectacle independence increases, the features of FLACS are highly relevant, especially when considering the implantation of premium intraocular lenses, such as toric, enhanced depth-of-focus, or multifocal lenses. The present article reviews the state of the art of femtosecond laser-assisted cataract (lens) surgery, contemplating the advantages and limitations of the two types of femtosecond laser pulses available (high and low energy) by evaluating their reported outcomes and complications.

Pupil versus 1st Purkinje capsulotomy centration with femtosecond laser: Long term outcomes with a sinusoidal trifocal lens.

PURPOSE: To assess the role of femtosecond laser-assisted capsulotomy centration in the long-term intraocular positioning of a multifocal intraocular lens. DESIGN: Prospective comparative study. METHODS: A total of 60 eyes of 30 patients underwent femtosecond laser-assisted Refractive Lens Exchange (RLE). For every patient, capsulotomy centration was randomly performed according to pupil centre (PC) in one eye and first Purkinje reflex (FPR) in the other. The intraocular lens (IOL) positioning, visual acuities, spherical equivalent, internal aberrometry and quality of vision were assessed and compared at 3 years' follow-up between groups (PC and FPR). RESULTS: Intraocular lens positioning showed a statistically significant difference between groups, with a closer centration to the visual axis in the FPR patients (p < 0.001). Internal aberrometry showed higher values in the PC capsulotomy centration group (p < 0.01). CONCLUSIONS: FPR centered capsulotomy is associated to a closer centration of the IOL to the visual axis.

Helper T cell immunity in humans with inherited CD4 deficiency.

CD4+ T cells are vital for host defense and immune regulation. However, the fundamental role of CD4 itself remains enigmatic. We report seven patients aged 5-61 years from five families of four ancestries with autosomal recessive CD4 deficiency and a range of infections, including recalcitrant warts and Whipple's disease. All patients are homozygous for rare deleterious CD4 variants impacting expression of the canonical CD4 isoform. A shorter expressed isoform that interacts with LCK, but not HLA class II, is affected by only one variant. All patients lack CD4+ T cells and have increased numbers of TCRαß+CD4-CD8- T cells, which phenotypically and transcriptionally resemble conventional Th cells. Finally, patient CD4-CD8- αß T cells exhibit intact responses to HLA class II-restricted antigens and promote B cell differentiation in vitro. Thus, compensatory development of Th cells enables patients with inherited CD4 deficiency to acquire effective cellular and humoral immunity against an unexpectedly large range of pathogens. Nevertheless, CD4 is indispensable for protective immunity against at least human papillomaviruses and Trophyrema whipplei.

CNS involvement and treatment with interferon-α are independent prognostic factors in Erdheim-Chester disease: a multicenter survival analysis of 53 patients.

Erdheim-Chester disease (ECD) is a rare form of non-Langerhans histiocytosis, with noncodified therapeutic management and high mortality. No treatment has yet been shown to improve survival in these patients. We conducted a multicenter prospective observational cohort study to assess whether extraskeletal manifestations and interferon-α treatment would influence survival in a large cohort of ECD patients. To achieve this goal, we thoroughly analyzed the clinical presentation of 53 patients with biopsy-proven ECD, and we performed a survival analysis using Cox proportional hazard model. Fifty-three patients (39 men and 14 women) with biopsy-proven ECD were followed up between November 1981 and November 2010. Forty-six patients (87%) received interferon-α and/or PEGylated interferon-α. Multivariate survival analysis using Cox proportional hazard model revealed that central nervous system involvement was an independent predictor of death (hazard ratio = 2.51; 95% confidence interval, 1.28-5.52; P = .006) in our cohort. Conversely, treatment with interferon-α was identified as an independent predictor of survival (hazard ratio = 0.32; 95% confidence interval, 0.14-0.70; P = .006). Although definitive confirmation would require a randomized controlled trial, these results suggest that interferon-α improves survival in ECD patients. This may be seen as a significant advance, as it is the first time a treatment is shown to improve survival in this multisystemic disease with high mortality.

Cataract Grade and Pupil: Comparison Between Conventional Phacoemulsification and Low-Energy Femtosecond Laser Assisted Cataract Surgery.

Purpose: This study presents a comparison of pupil changes according to cataract grade between low-energy femtosecond laser-assisted cataract surgery (FLACS) and conventional phacoemulsification (CP) in the same patient. Patients and Methods: Data from surgical records from patients submitted to cataract surgery with CP in one eye and FLACS in the other were retrospectively reviewed. The inclusion criterion was both eyes of the same patient having the same cataract grade in accordance with Lens Opacity Classification System (LOCS) III. Total pupil variation (TPV) was measured after recorded images, with intraindividual comparison between techniques, according to cataract grade (≤3 and >3), age and cumulative dissipated energy (CDE). Results: The study included a total of 124 eyes of 62 patients (mean age 72.65 ± 7.64 years). Analysis showed a statistically significant difference in TPV between techniques in the grade ≤3 cataract group (0.08 ± 0.22 mm²; p=0.034), with less pupil narrowing with FLACS, but not in the grade >3 group (0.01 ± 0.23 mm²; p=0.849). Regarding CDE, a significant difference (p<0.001) was found between techniques in both softer and harder cataracts, with lower values for FLACS. Correlation between CDE and TPV was significant for CP (p=0.021) but not for FLACS (p=0.922). TPV was significantly lower in older patients (age >74 years) for both techniques (p<0.001). Conclusion: There was a statistically significant difference between techniques (although of mild clinical relevance), with less reduction of pupil area with FLACS in softer cataracts (grade ≤3), as compared to CP. Higher levels of CDE are associated with more pupil narrowing in CP.

Pupil Status with Low-Energy Femtosecond Laser-Assisted Cataract Surgery versus Conventional Phacoemulsification: An Intraindividual Comparative Study.

Purpose: To compare the pupil changes in low-energy femtosecond laser-assisted cataract surgery (FLACS) with conventional phacoemulsification (CP) intraindividually. Patients and Methods: A retrospective review of registered surgical data from patients that undergone uncomplicated cataract surgery in a single centre, with randomly assigned femtosecond laser-assisted cataract surgery (FLACS) to one eye and conventional phacoemulsification (CP) to the other, was performed. The recorded pupil images were evaluated at pre and post laser treatment (after suction release) and at several surgical timepoints for both techniques (FLACS and CP). Pupil areas were calculated and compared in the same eye undergone FLACS (pre vs post laser treatment), between eyes (CP vs FLACS) in the same patient and between groups. Subgroups were built regarding age and ocular comorbidity. Results: This study involved a total of 164 eyes of 82 patients (55 female, 27 male). No statistical differences regarding the total duration of surgery (p=0.805) between FLACS and CP. Pupil measurements between pre and post laser treatment in the FLACS group showed no statistically significant differences (p=0.107). The mean change in pupil area from the beginning until the end of surgery (total variation) was 6.59±2.08 mm2 in the FLACS group and 6.67±2.13 mm2 in the CP group, associated to less narrowing of pupil area with FLACS, although not statistically significant (p=0.080). Comorbidity group analysis revealed less, but not significant, pupil narrowing with the FLACS technique (p=0.071). No statistically significant differences between FLACS and CP concerning age subgroups were registered. Conclusion: This study shows no significant pupil changes, namely myosis, after low-energy FLACS pre-treatment. Comparison between techniques showed less pupil variation in FLACS as compared to CP, more markedly in eyes with comorbidities (particularly with shallow anterior chamber), although non-statistically significant.

Orthostatic hypotension as an unusual presentation of spinal calcium pyrophosphate deposition disease: case report and review of literature.

Calcium pyrophosphate crystal deposition disease (CPPD), also known as pseudogout, with spinal involvement, is associated with clinical manifestations of acute nerve compression or chronic spinal stenosis. Precipitation of crystals of calcium pyrophosphate dihydrate in connective tissues can lead to acute inflammatory arthritis, degenerative chronic arthropathies, and radiographic evidence of cartilage calcification. We present a case of an 87-year-old woman, with unstudied chronic polyarthralgia and symptomatic orthostatic hypotension. It were documented acute calcium pyrophosphate deposition wrist arthritis, and cervical CT and MRI was suggestive of spinal involvement of CPPD. Workup excluded other causes of OH. Surgical approach could be indicated to minimize the symptoms, but it was contra-indicated due to the patient's performance status, so histological diagnosis was not possible. Muscle atrophy played an important part in the rapid progression of this insidious chronic disease. Conservative and symptomatic treatment achieve scarce short-term clinical improvement. Spinal involvement of CPPD was thought to be rare but recent studies show a higher prevalence than expected. We call for attention to the extent of structural changes that may occur when not early diagnosed nor treated. High clinical suspicion is required and this is, to our knowledge, the first report of orthostatic hypotension as a presentation of CPPD.

Bilensectomy: Safety and Visual Outcomes in Angle-Supported, Iris-Fixated, and Posterior Chamber Phakic Intraocular Lenses.

PURPOSE: To report the visual and refractive outcomes, intraoperative and postoperative complications, and main causes of bilensectomy in the different types of phakic intraocular lenses (pIOLs). METHODS: This was a retrospective multicenter study that included 234 eyes of 185 patients that underwent bilensectomy. Patients were divided into three groups depending on the pIOL that was explanted (angle-supported, iris-fixated, or posterior chamber). The main reasons leading to the indication for bilensectomy, time elapsed between pIOL implantation and bilensectomy, intraoperative and postoperative complications, uncorrected and corrected distance visual acuity (UDVA and CDVA), and endothelial cell density loss 1 year after bilensectomy were evaluated. RESULTS: There was a statistically significant improvement in UDVA and CDVA after bilensectomy in all groups. Cataract development was the main reason for bilensectomy, followed by significant endothelial cell density loss. Time between pIOL implantation and bilensectomy was significantly greater in eyes with an anterior chamber pIOL. CONCLUSIONS: Bilensectomy outcomes in general are good. Iris-fixated lenses, particularly hyperopic, are more prone to intraoperative complications and endothelial cell loss than the other pIOLs models. The results show that bilensectomy is a safe and effective procedure with a relatively low rate of intraoperative and postoperative complications and acceptable refractive predictability. [J Refract Surg. 2023;39(3):128-134.].

Distinct phenotypes in a cohort of anti-CASPR2 associated neurological syndromes.

INTRODUCTION: Anti-contactin-associated protein-like 2 (CASPR2) is classically associated with limbic encephalitis (LE), Morvan syndrome and peripheral nerve hyperexcitability (PNH). Additional clinical features have been previously recognized. OBJECTIVE: To describe a cohort of patients with anti-CASPR2-associated neurological syndromes from a tertiary referral centre. METHODS: Retrospective analysis of patients with positive serum anti-CASPR2 antibodies in the period between 2014 and 2021. RESULTS: Nineteen patients were identified, 11 (57.9%) male, with a median age at symptom onset of 49.0 (31.3-63.0) years and a median time to diagnosis of 1.0 (0.0-1.8) years. The most common clinical syndromes were LE (7 cases, 36.8%), Morvan syndrome (4, 21.1%) and PNH (2, 10.5%). Six patients presented with atypical phenotypes (31.6%), comprising dysautonomia (orthostatic hypotension and Adie's Pupil), motor tics/stereotypies, obsessive-compulsive disorder, and brainstem involvement. The most common presenting symptoms were seizures (31.6%), PNH (21.1%) and cognitive dysfunction (15.8%). One LE patient had a disease duration of 2,5 years and was initially diagnosed with dementia. CSF was normal in most cases. Brain MRI showed temporal lobe hyperintensities in 4 LE cases (57.1%). All PNH cases had myokymic discharges of fasciculations in the electromyography. Two patients had associated thymoma and 1 had lung adenocarcinoma. Eight patients (42.1%) received treatment during the acute phase and 26.3% maintenance treatment. Approximately half of the treated cases improved or stabilised, with 4 (21.1%) deaths in the whole cohort. CONCLUSION: Anti-CASPR2-associated neurological disorders may present with isolated atypical phenotypes, a slowly progressive clinical course, and with normal CSF or imaging findings.

Biologic therapy in large and small vessels vasculitis, and Behçet's disease: Evidence- and practice-based guidance.

OBJECTIVE: Vasculitis are a very heterogenous group of systemic autoimmune diseases, affecting large vessels (LVV), small vessels or presenting as a multisystemic variable vessel vasculitis. We aimed to define evidence and practice-based recommendations for the use of biologics in large and small vessels vasculitis, and Behçet's disease (BD). METHODS: Recommendations were made by an independent expert panel, following a comprehensive literature review and two consensus rounds. The panel included 17 internal medicine experts with recognized practice on autoimmune diseases management. The literature review was systematic from 2014 until 2019 and later updated by cross-reference checking and experts' input until 2022. Preliminary recommendations were drafted by working groups for each disease and voted in two rounds, in June and September 2021. Recommendations with at least 75% agreement were approved. RESULTS: A total of 32 final recommendations (10 for LVV treatment, 7 for small vessels vasculitis and 15 for BD) were approved by the experts and several biologic drugs were considered with different supporting evidence. Among LVV treatment options, tocilizumab presents the higher level of supporting evidence. Rituximab is recommended for treatment of severe/refractory cryoglobulinemic vasculitis. Infliximab and adalimumab are most recommended in treatment of severe/refractory BD manifestations. Other biologic drugs can be considered is specific presentations. CONCLUSION: These evidence and practice-based recommendations are a contribute to treatment decision and may, ultimately, improve the outcome of patients living with these conditions.

Different relationships between epilepsy syndromes and autoimmune diseases.

OBJECTIVE: Our objective was to study the relationship between epilepsy and autoimmune diseases in two different types of epilepsy: idiopathic generalized epilepsies (IGEs) and mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE-HS). The contribution of the human leukocyte antigen (HLA) system to this relationship was analyzed. METHODS: Adult patients with IGEs and MTLE-HS at a tertiary epilepsy center were consecutively enrolled between January 2016 and December 2020. RESULTS: A total of 664 patients, 422 with IGEs and 242 with MTLE-HS, were included. Patients with IGEs were 15 years younger, on average, than patients with MTLE-HS (p < .001). The frequency of autoimmune diseases was 5.5% (n = 23) and 4.5% (n = 11) in patients with IGEs and MTLE-HS, respectively (p = .716). The mean age of autoimmune disease onset was 20 ± 15.6 years in patients with IGEs and 36.7 ± 16.5 years in patients with MTLE-HS (p < .05). Clinical manifestations of autoimmune diseases preceded epilepsy onset in 30.4% of patients with IGEs (i.e., in early childhood); in the other patients, epilepsy appeared before autoimmune disease onset. In all but one patient with MTLE-HS and autoimmune diseases, the autoimmune diseases appeared after epilepsy onset from adolescence onward. SIGNIFICANCE: Our study indicates two relationship patterns: a bidirectional association between IGEs and autoimmune diseases and a unidirectional relationship between MTLE-HS and autoimmune diseases. The involvement of genetic susceptibility factors (such as the HLA system), autoinflammatory mechanisms, female sex, and antiseizure medications in these relationships are discussed.

Host-derived mannose glycans trigger a pathogenic γδ T cell/IL-17a axis in autoimmunity.

Autoimmune diseases are life-threatening disorders that cause increasing disability over time. Systemic lupus erythematosus (SLE) and other autoimmune diseases arise when immune stimuli override mechanisms of self-tolerance. Accumulating evidence has demonstrated that protein glycosylation is substantially altered in autoimmune disease development, but the mechanisms by which glycans trigger these autoreactive immune responses are still largely unclear. In this study, we found that presence of microbial-associated mannose structures at the surface of the kidney triggers the recognition of DC-SIGN-expressing γδ T cells, inducing a pathogenic interleukin-17a (IL-17a)-mediated autoimmune response. Mice lacking Mgat5, which have a higher abundance of mannose structures in the kidney, displayed increased γδ T cell infiltration into the kidney that was associated with spontaneous development of lupus in older mice. N-acetylglucosamine supplementation, which promoted biosynthesis of tolerogenic branched N-glycans in the kidney, was found to inhibit γδ T cell infiltration and control disease development. Together, this work reveals a mannose-γδ T cell-IL-17a axis in SLE immunopathogenesis and highlights glycometabolic reprogramming as a therapeutic strategy for autoimmune disease treatment.

Biological therapy in systemic lupus erythematosus, antiphospholipid syndrome, and Sjögren's syndrome: evidence- and practice-based guidance.

Systemic lupus erythematosus (SLE), antiphospholipid syndrome (APS), and Sjögren's syndrome (SS) are heterogeneous autoimmune diseases. Severe manifestations and refractory/intolerance to conventional immunosuppressants demand other options, namely biological drugs, and small molecules. We aimed to define evidence and practice-based guidance for the off-label use of biologics in SLE, APS, and SS. Recommendations were made by an independent expert panel, following a comprehensive literature review and two consensus rounds. The panel included 17 internal medicine experts with recognized practice in autoimmune disease management. The literature review was systematic from 2014 until 2019 and later updated by cross-reference checking and experts' input until 2021. Preliminary recommendations were drafted by working groups for each disease. A revision meeting with all experts anticipated the consensus meeting held in June 2021. All experts voted (agree, disagree, neither agree nor disagree) during two rounds, and recommendations with at least 75% agreement were approved. A total of 32 final recommendations (20 for SLE treatment, 5 for APS, and 7 for SS) were approved by the experts. These recommendations consider organ involvement, manifestations, severity, and response to previous treatments. In these three autoimmune diseases, most recommendations refer to rituximab, which aligns with the higher number of studies and clinical experience with this biological agent. Belimumab sequential treatment after rituximab may also be used in severe cases of SLE and SS. Second-line therapy with baricitinib, bortezomib, eculizumab, secukinumab, or tocilizumab can be considered in SLE-specific manifestations. These evidence and practice-based recommendations may support treatment decision and, ultimately, improve the outcome of patients living with SLE, APS, or SS.

[Emery-Dreifuss muscular dystrophy: case report]. / Distrofia muscular de Emery-Dreifuss: a propósito de um caso clínico.

Emery-Dreifuss muscular dystrophy type 1 (EDMD1) is a familial disease with X-Linked recessive transmission, caused by a mutation in a nuclear envelope protein, emerin. Clinical manifestations usually occur in adolescence and include contractures, muscle atrophy and weakness, and cardiac conduction disturbances. We describe the case of a young male, aged 16, with first-degree atrioventricular (AV) block and limited extension of both forearms. He had elevated CK, and cardiac monitoring showed severe conduction tissue disease, with significant sinus pauses, chronotropic incompetence and periods of AV dissociation during exercise. Immunohistochemical staining using an emerin antibody showed absence of the protein in a fragment of muscle tissue and genetic study identified a mutation associated with EDMD1. Study of his brother, aged 21, also established a diagnosis of EDMD1. Both individuals received a permanent pacemaker but musculoskeletal manifestations at that time did not warrant any other intervention: Screening for certain genetic diseases, including muscular dystrophies, is mandatory following identification of conduction abnormalities in young people.