Organ-specific Autoimmune Diseases Research Articles

Autoimmune CD8+ T cells in type 1 diabetes: from single-cell RNA sequencing to T-cell receptor redirection

Type 1 diabetes (T1D) is an organ-specific autoimmune disease caused by pancreatic β cell destruction and mediated primarily by autoreactive CD8+ T cells. It has been shown that only a small number of stem cell-like β cell-specific CD8+ T cells are needed to convert normal mice into T1D mice; thus, it is likely that T1D can be cured or significantly improved by modulating or altering self-reactive CD8+ T cells. However, stem cell-type, effector and exhausted CD8+ T cells play intricate and important roles in T1D. The highly diverse T-cell receptors (TCRs) also make precise and stable targeted therapy more difficult. Therefore, this review will investigate the mechanisms of autoimmune CD8+ T cells and TCRs in T1D, as well as the related single-cell RNA sequencing (ScRNA-Seq), CRISPR/Cas9, chimeric antigen receptor T-cell (CAR-T) and T-cell receptor-gene engineered T cells (TCR-T), for a detailed and clear overview. This review highlights that targeting CD8+ T cells and their TCRs may be a potential strategy for predicting or treating T1D.

Puerarin Alleviates Experimental Autoimmune Thyroiditis by Regulating Macrophages.

Hashimoto's thyroiditis (HT) is the most common organ-specific autoimmune disease, predominantly affecting women. Although the pathogenesis of HT is incompletely understood, some studies have found that macrophage polarization plays a role. Puerarin is a soy isoflavone compound that has anti-inflammatory and immunomodulatory effects and regulates macrophage immune activity. This study aimed to verify the therapeutic effect of puerarin on HT and explored its regulatory effect on macrophage polarization imbalance in HT. Through bioinformatics analysis and molecular biology methods, it was found that macrophages increased significantly in HT patients and model mice. Immunological staining showed that puerarin intervention could reduce tissue inflammatory cell infiltration. Molecular biological examination displayed that puerarin could inhibit local and systemic inflammation levels, and the expression of marker thyroglobulin and thyroid peroxidase Abs. In vivo experimental results indicated that puerarin regulated macrophage polarity and reduced inflammatory damage, possibly by inhibiting the pyroptosis signaling pathway. In vivo macrophage clearance experiments demonstrated that puerarin relied on macrophages to exert its mechanism of action in treating HT. The results of this study indicate that macrophages are important mediators in the development of HT, and puerarin can regulate macrophage polarity and inflammatory status to provide thyroid tissue protection, which provides a new idea for the treatment of HT.

Prevalence of autoimmune thyroiditis among children with autoimmune hepatitis.

Autoimmune hepatitis (AIH) is an organ specific autoimmune disease, which can manifest at any age of life. there is a high prevalence of extrahepatic autoimmune diseases in patients with AIH. Autoimmune thyroid diseases (ATDs) are the most frequent extrahepatic autoimmune disorders among patients with AIH. Aim of work is to detect the frequency of ATDs among Egyptian children with AIH. This research is a cross-sectional study conducted on 58 children with AIH aged ≤ 18years. All patients were tested for free triiodothyronine (FT3), free tetraiodothyronine (FT4), thyroid stimulating hormone (TSH), anti-thyroid peroxidase (anti-TPO) and antithyroglobulin (anti-TG). Thyroid ultrasound (US) and thyroid scan were performed for patients with abnormal thyroid profile, borderline values, positive anti-TPO or anti-TG. The mean ± standard deviation (SD) for the age of the patients was 11.3 ± 4.5years. Out of 58 patients of AIH, 28 patients (48.3%) had associated other autoimmune diseases. Autoimmune thyroiditis was the most common associated autoimmune disease being present in 10 patients (17.2%). The thyroid status of AIT patients showed that 6 patients (60%) were euthyroid, 3 patients (30%) had subclinical hypothyroidism and only one patient (10%) was hyperthyroid. Autoimmune hepatitis in Egyptian children is commonly associated with other autoimmune diseases. Autoimmune thyroiditis is the most common to be associated with AIH in pediatric patients. As it is not usually clinically manifesting, regular screening for AIT in children with AIH is mandatory.

Immune Regulatory Effects of Sinomenine on Primary Membranous Nephropathy: Based on Case Report and Network Pharmacology

PMN an organ-specific autoimmune disease, is the leading cause of nephrotic syndrome (NS) in adults worldwide. However, there is no specific treatment for PMN other than optimal supportive care in low and moderate risk PMN. Immunosuppressive therapy is restricted to patients considered at risk for progressive kidney injury.

Association of autoimmune thyroid disease with type 1 diabetes mellitus and its ultrasonic diagnosis and management.

As a common hyperglycemic disease, type 1 diabetes mellitus (T1DM) is a complicated disorder that requires a lifelong insulin supply due to the immune-mediated destruction of pancreatic β cells. Although it is an organ-specific autoimmune disorder, T1DM is often associated with multiple other autoimmune disorders. The most prevalent concomitant autoimmune disorder occurring in T1DM is autoimmune thyroid disease (AITD), which mainly exhibits two extremes of phenotypes: hyperthyroidism [Graves' disease (GD)] and hypo-thyroidism [Hashimoto's thyroiditis, (HT)]. However, the presence of comorbid AITD may negatively affect metabolic management in T1DM patients and thereby may increase the risk for potential diabetes-related complications. Thus, routine screening of thyroid function has been recommended when T1DM is diagnosed. Here, first, we summarize current knowledge regarding the etiology and pathogenesis mechanisms of both diseases. Subsequently, an updated review of the association between T1DM and AITD is offered. Finally, we provide a relatively detailed review focusing on the application of thyroid ultrasonography in diagnosing and managing HT and GD, suggesting its critical role in the timely and accurate diagnosis of AITD in T1DM.

Is There a Link between Thyroid Peroxidase Gene Promoter Polymorphisms and Autoimmune Thyroiditis in the Polish Population?

(1) Autoimmune thyroiditis (AIT) is the most common cause of primary hypothyroidism and one of the most frequent organ-specific autoimmune diseases. Its pathogenesis is polygenic and still requires further research. The aim of the study was to assess, for the first time in the Caucasian population, the role of selected TPO gene promoter polymorphisms (rs2071399 G/A, rs2071400C/T, rs2071402 A/G, and rs2071403 A/G) in the development of AIT. A total of 237 patients diagnosed with AIT and 130 healthy controls were genotyped for four TPO gene polymorphisms, and the results were statistically analyzed to check for the role of these polymorphisms. There were no significant differences in the genotype and allele frequencies of the studied TPO gene promoter polymorphisms between patients and controls (p > 0.05). The haplotype distribution (rs2071400-rs2071402-rs2071403) between the two studied groups was similar for the most common variants (CGA, CAG, TGG). Only a rare haplotype (CGG) occurred more frequently among patients compared to controls (p = 0.04). The studied TPO gene promoter polymorphisms did not show an association with susceptibility to AIT in the Caucasian Polish population, contrary to the results in Japanese patients.

Preliminary Study on Total Glucoside of Peony (TGP) Administration in Organ-Specific Autoimmune Diseases at Prof. dr. R. D. Kandou Hospital, Indonesia

Autoimmune diseases are a diverse group of conditions characterized by immune disturbances that cause aberrant B cell and T cell reactivity to normal constituents of the host. These diseases can involve essentially any organ system and affect individuals of any age, with a much greater prevalence among women. Although certain mechanisms unite these conditions into a single category, the clinical manifestations of autoimmune disease are highly varied. This research is an original and interventional study. It is a preliminary with analytic observational. The design is “the one group pre-test – post-test design”. This study was conducted at RSUP Prof. dr. R. D. Kandou over a six-month period from July 2016 to December 2016. The study included patients diagnosed with Graves’ disease, Hashimoto’s disease, and aplastic anemia, who were diagnosed based on their medical history, physical examination, and diagnostic workups. This study also aimed to evaluate the improvement in clinical symptoms within the Aplastic Anemia group, tracking the number of complaints reported each week. Four patients were included in the study, each receiving individualized basic therapy.

Retrospective Analysis of the Effect of Comorbid Atopic Dermatitis on the Treatment Response to Topical Immunotherapy in Pediatric Alopecia Areata Patients.

Alopecia areata is an organ-specific autoimmune disease. In addition, treatment options are limited in pediatric patients. Topical immunotherapy treatment may be preferred, especially in pediatric patients with severe and/or refractory alopecia areata. In this study, it was aimed to examine the effect of atopic dermatitis, which is one of the poor prognostic factors in pediatric alopecia areata, on topical immunotherapy treatment. The data of patients aged 18 years and younger who received at least 20 sessions of topical immunotherapy with the diagnosis of alopecia areata in our clinic between January 2018 and December 2020 were analyzed. A total of 139 patients were included in the study. The mean age of the patients was 10.29 years, 67 (48.20%) of the patients were female, 72 (51.80%) were male, 24 (17.26%) of the patients had mild disease, 115 of them (82.73%) had severe disease. Atopic dermatitis accompanying alopecia areata was detected in 38 of the patients. Inadequate response was obtained in 60 (43.17%) patients and adequate response was obtained in 79 (56.83%) patients with topical immunotherapy treatment. In addition, the presence of atopic dermatitis in the patient group with inadequate response to treatment was found to be statistically significantly higher than the patient group with adequate response to treatment. Topical immunotherapy treatment was found to be effective in 56.83% of pediatric alopecia areata patients included in the study. Our study showed that questioning pediatric alopecia areata patients for atopic dermatitis before topical immunotherapy treatment can predict the response to treatment.

Effects of iodine intake on gut microbiota and gut metabolites in Hashimoto thyroiditis-diseased humans and mice

Hashimoto thyroiditis (HT) is an organ-specific autoimmune disease linked to iodine intake. Emerging evidence highlights the gut microbiota’s role in HT pathogenesis via the microbiota-gut-thyroid axis. However, the process through which iodine intake modifies the microbiota and triggers HT remains unclear. This study examines how iodine affects gut dysbiosis and HT, recruiting 23 patients with HT and 25 healthy individuals to assess gut microbiota composition and metabolic features. Furthermore, we establish a spontaneously developed thyroiditis mouse model using NOD.H-2h4 mice highlighting the influence of iodine intake on HT progression. The butanoate metabolism significantly differs between these two groups according to the enrichment results, and butyric acid is significantly decreased in patients with HT compared with those in healthy individuals. Gut dysbiosis, driven by excessive iodine intake, disrupts TH17/Treg balance by reducing butyric acid. In summary, iodine intake alters intestinal microbiota composition and metabolic changes influencing the microbiota-gut-thyroid axis.

Roles of TRP and PIEZO receptors in autoimmune diseases.

Autoimmune diseases are pathological autoimmune reactions in the body caused by various factors, which can lead to tissue damage and organ dysfunction. They can be divided into organ-specific and systemic autoimmune diseases. These diseases usually involve various body systems, including the blood, muscles, bones, joints and soft tissues. The transient receptor potential (TRP) and PIEZO receptors, which resulted in David Julius and Ardem Patapoutian winning the Nobel Prize in Physiology or Medicine in 2021, attracted people's attention. Most current studies on TRP and PIEZO receptors in autoimmune diseases have been carried out on animal model, only few clinical studies have been conducted. Therefore, this study aimed to review existing studies on TRP and PIEZO to understand the roles of these receptors in autoimmune diseases, which may help elucidate novel treatment strategies.

IMoVR-Net: A robust interpretable network for multi-ocular lesion recognition from TAO facial images

Thyroid-associated ophthalmopathy (TAO) is an organ-specific autoimmune disease that seriously affects patient's life and health. However, the early diagnosis of TAO is highly dependent on the physician's subjective experience. Moreover, the currently proposed deep learning networks for eye diseases do not provide robust interpretability concerning feature learning paradigm, model structure, and the number of neurons. But the mentioned components are very important for model interpretability and are key factors that severely affect the transparency of the model. Therefore, a robust interpretable multi-orientation visual recognition network (IMoVR-Net) for TAO multi-ocular lesion recognition is proposed in this paper. Firstly, a multi-orientation visual cascaded encoder composed of the DenseGabor module and the dilated Gabor convolution group is proposed to achieve the fine extraction of multi-directional TAO lesion features by using a novel feature learning paradigm called alternating filtering. Besides, combining information theory and topology tool, an optimization rule based on topological energy entropy is proposed to provide a solid interpretable theory for determining the model structure. Finally, a clustering correlation analysis method is developed to accomplish the determination of the number of convolutional hidden neurons, providing robust interpretability for the selection of the number of neurons. Compared to other advanced models, the IMoVR-Net achieved state-of-the-art performance on different TAO ocular datasets with an average accuracy, sensitivity, precision, and F1 score of 0.878, 87.27 %, 0.875, and 87.39 %, respectively. The IMoVR-Net has good clinical application prospects due to its strong recognition ability and robust interpretability in feature extraction paradigm, model structure, and number of convolutional neurons.

Biomarker MSC-C5b-9-Guided Master Therapies for Resistant/Recurrent ITP: A Prospective, Randomized, Open-Label, Multicenter Trial

Introduction: Immune thrombocytopenia (ITP) is an acquired organ-specific autoimmune disorder and a common bleeding disorder that poses a considerable risk to human health. Steroids, as the first-line treatment, do not provide long-term relief. Our previous clinical trials have confirmed the efficacy and safety of all-trans retinoic acid (ATRA) in the treatment of ITP and identified that the biomarker MSC-C5b-9 may be a stratification marker for evaluating the efficacy of ATRA (Haematologica, 2019; Lancet Haematol. 2017; 2021). This research aims to develop a new treatment approach for steroid-resistant/recurrent ITP based on the marker MSC-C5b-9. Method: We conducted a prospective, randomized, open-label, multicenter trial to evaluate the efficacy and safety of ATRA combined with eltrombopag based on MSC-C5b-9 as a novel treatment for steroid-resistant/recurrent ITP. Following enrollment, all patients underwent bone marrow aspiration to assess MSC-C5b-9 levels. Subsequently, patients were randomly assigned in a 1:1 ratio to either the eltrombopag group or the eltrombopag + ATRA group. In both treatment groups, the initial dose of eltrombopag was 50 mg daily, with dose adjustments based on platelet levels. For patients assigned to the ATRA group, ATRA was given at a dose of 10 mg twice daily. Peripheral blood cell counts and adverse drug reactions were regularly monitored. The primary endpoint was the sustained response rate at 18 months after randomization, and secondary endpoints include Complete Remission, Partial Remission, Relapse rate, Early Response, Initial Response, Adverse Events, and Adverse Events graded using the National Cancer Institute Common Terminology Criteria (NCI CTCAE) v5.0 criteria. The study has been registered at clinicaltrials.gov. NCT05438875. Result: From March 2023 to July 2023, a total of 30 patients with steroid-resistant/recurrent ITP were enrolled in the study and randomized 1:1 to receive eltrombopag combined with ATRA (ATRA group, n=15, MSC-C5b-9 +6, -9) or eltrombopag alone (control group, n=15, MSC-C5b-9 +6, -9) in 5 centers, and all enrolled patients were included in the intention-to-treat (ITT) analysis. In the ATRA group, the median age was 38 years (range, 29-64), consisting of 8 male patients. In the control group, the median age was 44 years (range, 23-75), consisting of 9 male patients. There were no statistically significant differences observed in the baseline clinical characteristics between the two groups. There was no difference in the bleeding score and ECOG score between the two groups (P=0.717; P=1.000). The median platelet count was comparable between the ATRA group and the control group (17 (1-28) vs. 16 (2-26), P=0.850). Comorbidities at random, such as hypertension, were comparable between the two groups (26.7% (4/15) vs. 33.3% (5/15), P=1.000). Combined autoantibody abnormalities were compared between the two groups (6.7% (1/15) vs. 6.7% (1/15), P=1.000). The rate of Early Response in the ATRA group was higher than that in the control group, but the difference was not significant (73.3% (11/15) vs. 53.5% (8/15), P=0.256). As of July 29, 2023, a total of 24 patients had been enrolled for a duration exceeding 4 weeks. Similarly, the Initial Response rate was higher in the ATRA group, but no significant difference was observed between the two groups (84.6% (11/13) vs. 63.6% (7/11), P=0.357). Nevertheless, it is noteworthy that the 4-week CR rate in the ATRA group was higher than that in the control group (76.9% (10/13) vs. 36.4% (4/11), P=0.045). What's more, the overall efficacy of the ATRA group was better than that of the control group. The mean platelet count at weeks 1, 2, 3, and 4 posttreatment, along with the mean maximum platelet count posttreatment, exhibited higher values in the ATRA group than in the control group; however, these disparities did not reach statistical significance (P=0.310; P=0.568; P=0.779; P=0.618; P=0.355). ATRA was well tolerated, and only one patient developed grade I dry mouth and headache, which improved after dose reduction. There was no difference between the ATRA and control groups in terms of medication adverse effects (13.3% (2/15) vs. 13.3% (2/15), P=1.000). Conclusions: Eltrombopag plus ATRA is an effective and well-tolerated approach for treating steroid-resistant/recurrent ITP. Eltrombopag plus ATRA can enhance patients' complete remission and is well tolerated.

[Pemphigus: current and future treatment strategies].

Pemphigus diseases are agroup of organ-specific autoimmune diseases which are characterised by the production of autoantibodies against intra-epidermal adhesion molecules and structural proteins of skin and mucosae. Depending on the entity, patients develop blisters and erosions on the skin and/or mucosae. According to the AWMFS2k guidelines for diagnosis and therapy of pemphigus diseases, a systemic therapy is recommended. Initially, high-dose, oral corticosteroids in combination with immunosuppressive drugs as corticosteroid-sparing agent, usually azathioprine or mycophenolate mofetil, can be used. Furthermore, rituximab, amonoclonal antibody directed against CD20 on Bcells, was recently approved for pemphigus vulgaris and moderate or severe pemphigus foliaceus.

Innate Immunity in Autoimmune Thyroid Disease during Pregnancy.

Autoimmune thyroid disease (AITD) is the most common organ-specific autoimmune disorder clinically presented as Hashimoto thyroiditis (HT) and Graves' disease (GD). The pathogenesis of AITD is caused by an inappropriate immune response related to genetic, non-genetic, and environmental factors. Pregnancy is one of the factors that have a great influence on the function of the thyroid gland because of the increased metabolic demand and the effects of hormones related to pregnancy. During pregnancy, an adaptation of the maternal immune system occurs, especially of the innate immune system engaged in maintaining adaptive immunity in the tolerant state, preventing the rejection of the fetus. Pregnancy-related hormonal changes (estrogen, progesterone, hCG) may modulate the activity of innate immune cells, potentially worsening the course of AITD during pregnancy. This especially applies to NK cells, which are associated with exacerbation of HD and GD. On the other hand, previous thyroid disorders can affect fertility and cause adverse outcomes of pregnancy, such as placental abruption, spontaneous abortion, and premature delivery. Additionally, it can cause fetal growth retardation and may contribute to impaired neuropsychological development of the fetus. Therefore, maintaining the thyroid equilibrium in women of reproductive age and in pregnant women is of the highest importance.

Identification of optimal feature genes in patients with thyroid associated ophthalmopathy and their relationship with immune infiltration: a bioinformatics analysis.

Thyroid associated ophthalmopathy (TAO) is an organ-specific autoimmune disease that has a significant impact on individuals and society. The etiology of TAO is complicated and poorly understood. Thus, the goal of this study was to use bioinformatics to look into the pathogenesis of TAO and to identify the optimum feature genes (OFGs) and immune infiltration patterns of TAO. Firstly, the GSE58331 microarray data set was utilized to find 366 differentially expressed genes (DEGs). To find important modular genes, the dataset was evaluated using weighted gene coexpression network analysis (WGCNA). Then, the overlap genes of major module genes and DEGs were further assessed by applying three machine learning techniques to find the OFGs. The CIBERSORT approach was utilized to examine immune cell infiltration in normal and TAO samples, as well as the link between optimum characteristic genes and immune cells. Finally, the related pathways of the OFGs were predicted using single gene set enrichment analysis (ssGSEA). KLB, TBC1D2B, LINC01140, SGCG, TMEM37, and LINC01697 were the six best feature genes that were employed to create a nomogram with high predictive performance. The immune cell infiltration investigation revealed that the development of TAO may include memory B cells, T cell follicular helper cells, resting NK cells, macrophages of type M0, macrophages of type M1, resting dendritic cells, active mast cells, and neutrophils. In addition, ssGSEA results found that these characteristic genes were closely associated with lipid metabolism pathways. In this research, we found that KLB, TBC1D2B, LINC01140, SGCG, TMEM37, and LINC01697 are intimately associated with the development and progression of TAO, as well as with lipid metabolism pathways.

FRI544 Serological Profile In Rheumatoid Arthritis And Its Interplay With Autoimmune Thyroid Diseases

Abstract Disclosure: T. Kolitz: None. S. Kivity: None. I. Tessler: None. Y. Marcus-Perlman: None. E. Izkhakov: None. I. Yaish: None. Y. Greenman: None. Objective: Autoimmune thyroid diseases (AITD) are the most common organ-specific autoimmune disorders, with an estimated prevalence of 5%. AITD encompass the clinical scope of Hashimoto’s thyroiditis (HT) and Graves’s disease (GD). Rheumatoid arthritis (RA) is a relatively common non-organ-specific autoimmune disease with an estimated global prevalence of 0.5-1%. Numerous studies have investigated the association of thyroid disorders and RA in various populations, but results were inconsistent. This study is aimed to assess the rate of AITD in RA patients and to further investigate these rates in subgroups of patients with seronegative RA, seropositive RA and dual-positive RA antibodies [i.e., positive anti-cyclic citrullinated peptide (CCP) and rheumatoid factor (RF)]. Methods: We used a big-data platform (MDClone Ltd., Israel) to create a cohort of RA patients with and without coexistent AITD. The cohort included 1316 patients who were treated in the Tel Aviv Sourasky Medical Center for any diagnosis between January 2008 and December 2022. Results: There were 340 men (25.8%) and 976 (74.2%) women in the cohort. The mean age at time of initial coding of RA diagnosis in our referral center was 62.5±15 years. AITD was found in 15.5% of the entire RA cohort. Hypothyroidism was the most common thyroid-associated diagnosis (in 95.8% of patients with RA and AITD). When RA patients were further sub-classified to seronegative, seropositive, and dual-positive RA, the rates of AITD were 11.8%, 17.6% and 25%, respectively (p=0.007). AITD rates in seropositive women and men were 20.6% and 8%, respectively (p<0.001). In the RA-seronegative subgroup, the rate of AITD was 15.6% in women and 2.7% in men (p<0.001). The mortality rates in RA-seronegative patients, RA-seronegative patients with AITD, RA-seropositive patients and RA-seropositive patients with AITD were 5.5%, 8.3%, 21.6% and 29.5%, respectively (p=0.05). Conclusion: Our findings suggest that the prevalence of AITD in patients with RA is associated with the specific serological profile, with highest rates in RA patients who are positive for both anti-CCP and RF. Randomized prospective studies are required to explore any cause-and-effect correlation and to delineate the impact of AITD on RA outcome and mortality rates. Presentation: Friday, June 16, 2023

B-101 Aquaporin 4 and Neuromyelitis Optica Spectrum Disorders

Abstract Background Neuromyelitis óptica (NMO) is a rare demyelinating inflammatory disease of the central nervous system, characterized by acute optic neuritis (ON) and transverse myelitis (TM). Previously, it was considered as a variant of multiple sclerosis (MS), however, there are now several clinical, laboratory, neuroimaging and pathological anatomical features that distinguish it from MS as the presence of a specific autoantibody in blood called IgG-NMO or anti-AQP4 that binds to water channels named aquaporin-4 (AQP4) expressed on astrocytes and plays a key role in the pathogenesis of this disease. Some patients remain seronegative for AQP4-IgG despite a definite diagnosis of NMO and the use of the finest methods for antibody detection. In anti-AQP4 seronegative forms, antibodies against myelin oligodendrocyte glycoprotein (MOG) may be identified. We have carried out a review of those patients with anti-AQP4-IgG detected in the autoimmunity laboratory during the last 3 years. Methods Each year we receive an average of 260 samples from patients with suspected demyelinating pathology with or without visual impairment. For the detection of antibodies against AQP-4 specifically HEK293 cells transfected were used as the standard substrate. Anti-MOG antibody can be detected in the same test. Measurement range: The dilution starting point for this measurement system is 1:10 (serum/plasma) and 1:1 (CSF, undiluted). Results A total of 5 patients were positive for anti AQP-4 antibody in serum samples, all women aged between 23 and 78 years. All patients except the youngest, who presented to the neurology department for loss of visual acuity, had other autoimmune diseases: systemic lupus erythematosus (SLE) in conjunction with rheumatoid arthritis, SLE in conjunction with Graves’ disease and hypothyroidism, the two oldest (59 and 78 years), respectively. The oldest patient was admitted to the internal medicine department for persistent nausea, vomiting and hiccups and was diagnosed as NMO spectrum disorder. In all cases, the oligoclonal immunoglobulin G bands study in CSF was negative. None of the CSF samples tested were positive for anti AQP-4 antibody. All patients were treated with methylprednisolone, but treatment with azathioprine or rituximab was necessary in 3 patients. Conclusion Titers of antibodies against AQP-4 are significantly higher in serum than in CSF, with serum being the most sensitive simple. NMO is more prevalent in women than men, with a female predominance usually higher than observed in MS. The median age of onset is also higher than MS, with a median of 35–45 years. Since the discovery of AQ-4 antibodies, there has been an increase in the number of clinical and radiological manifestations of NMO beyond involvement of the optic nerve and the spinal cord, including manifestations in the brain. It is important to recognise them in order to make an early diagnosis, to avoid unnecessary complementary tests and to establish the most suitable treatment. Persistent and intractable hiccups and nausea may occur in 17%–43% as in our oldest patient’s case. Associations with organ-specific autoimmune diseases such as autoimmune thyroiditis, and non-organ-specific diseases such as SLE and Sjögren’s syndrome have been described.

Stiff-Leg Syndrome Associated with Autoimmune Retinopathy and Its Treatment with IVIg-A Case Report and Review of the Literature.

Antibodies to glutamic acid decarboxylase (GAD) have been predominantly associated with stiff-person syndrome (SPS), which is often accompanied by organ-specific autoimmune diseases, such as late-onset type 1 diabetes. Autoimmune retinal pathology in SPS has recently been suggested to coexist in patients suffering from this disease; however, evidence reporting potential treatment options for the neurological and visual symptoms these patients experience remains scarce. We provide a review of the relevant literature, presenting a rare case of a middle-aged woman with autoimmune retinopathy (AIR) followed by stiff-leg syndrome who responded to intravenous immune globulin treatment (IVIg). Our report adds to previously reported data supporting the efficacy of IVIg in SPS spectrum disorders while also proposing the potential effect of IVIg in treating SPS spectrum patients with coexisting AIR.

Intralesional Methotrexate for Treatment of Alopecia Areata: Clinical Evaluation and Effect on Lesional TNF Alpha

Abstract Background Alopecia areata (AA) is an organ-specific autoimmune disease characterized by T-cell infiltrates and cytokine production including tumor necrosis factor alpha (TNF-α). Methotrexate causes T cell apoptosis and adenosine release that involves inhibition of TNF-α that could be the mechanism of action in AA. Aim of the Work To assess the efficacy of intralesional methotrexate in the treatment of alopecia areata and study its effect on TNF alpha tissue levels compared to before. Patients and Methods 30 patients were injected by intralesional methotrexate every two weeks for 3 months and a scalp biopsy was taken before and after treatment to measure lesional TNF-α. Results There was significant hair regrowth after methotrexate treatment with significant decrease in lesional TNF-α. Conclusion Intralesional methotrexate is an effective treatment for alopecia areata with mechanism of action involving decrease of TNF-α.

Cataract Surgery Outcomes in Patients with Non-ocular Autoimmune Disease.

While phacoemulsification cataract extraction is generally highly effective and safe, patients with a history of uveitis are at higher risk for postoperative complications and often require a modified perioperative medication regimen. No data exists on risks of postoperative complications and persistent anterior uveitis (PAU) in patients with non-ocular autoimmune disease. Medical records were reviewed of patients who underwent phacoemulsification cataract surgery with intraocular lens implantation between January1, 2014 and December31, 2019 at the University of Colorado Hospital (UCH) as part of a retrospective cohort study. Exclusion criteria included patient history of ocular inflammation and cataract surgery combined with another intraocular surgery. Patients were only included as having autoimmune disease if the diagnosis was confirmed by a relevant specialist at UCH. Patients with autoimmune disease were then stratified into systemic versus organ-specific autoimmune disease, and patients with systemic autoimmune disease were further stratified into immunosuppressed and not immunosuppressed at the time of cataract surgery. Patients with PAU were identified according to the Standardization of Uveitis Nomenclature Working Group. Data including sex, race/ethnicity, intraoperative cumulative dissipated energy (CDE), and postoperative best-corrected visual acuity (BCVA) and intraocular pressure (IOP) were obtained. A total of 422 eyes from 248 patients had confirmed autoimmune disease, compared to a control group of 10,201 eyes. The autoimmune and systemic autoimmune disease groups were not more likely to have postoperative complications or PAU compared to the control group. Immunosuppression status among the systemic autoimmune disease group was also not associated with postoperative complications or PAU. Patients with non-ocular autoimmune disease do not appear to be at higher risk for postoperative complications, including worse BCVA or increased rates of IOP elevation and PAU, following phacoemulsification cataract surgery. These patients do not appear to require modification of the typical perioperative medication regimen.