Concurrent Autoimmune Diseases Research Articles

Prevalence of comorbid autoimmune diseases and antibodies in newly diagnosed multiple sclerosis patients

BackgroundDiagnosing multiple sclerosis (MS) is challenging due to diverse symptoms and the absence of specific biomarkers. Concurrent autoimmune diseases (AID) or non-specific antibodies further complicate diagnosis, progression monitoring, and management. Data on AID prevalence in MS patients are sparse. This study aims to identify concurrent AIDs alongside MS.MethodsIn this retrospective single-center study, we analyzed patient records at our university hospital from 2010 to 2017, focusing on cases suspected of inflammatory demyelinating disease. The 2017 McDonald criteria were applied. Additionally, we measured neurofilament light (NfL) levels from available CSF samples in our biobank.ResultsWe identified a total of 315 patients, of whom 66% were women. In total, 13.7% of all patients had concurrent AID, while 20.3% had isolated antibody findings without AID. The most common AID was autoimmune thyroiditis (8.9%), followed by chronic inflammatory skin diseases (1.6%), arthritis (1%), type 1 diabetes (1%), Sjögren’s syndrome (0.6%), and inflammatory bowel diseases (0.6%). Cardiolipin antibodies were the most frequent isolated antibody finding (8.6%). Our data showed that, from the perspective of the initial demyelinating event, neither comorbid AID nor isolated antibodies significantly influenced relapses or MS progression over a median follow-up of 9 months. Standard CSF parameters and NfL levels were similar between the groups at the time of MS diagnosis.ConclusionOur study shows that AIDs, particularly autoimmune thyroiditis, frequently occur at the onset of MS. The proportion of AIDs commonly treated with immunomodulatory therapy in our cohort was similar to that observed in the general population. Comorbid AID did not affect NfL levels, indicating similar disease activity. Future research should explore new AID emergence during the course of MS, especially considering the increased incidence of rheumatic diseases later in life.

Autoimmune Outcomes in Patients with Concurrent Autoimmune Disease Receiving CD19 CAR T-Cell Therapy for Lymphoma

Autoimmune Outcomes in Patients with Concurrent Autoimmune Disease Receiving CD19 CAR T-Cell Therapy for Lymphoma

The Incidence and Predictive Factors of Thromboembolism During Hospitalizations for Inflammatory Bowel Disease Flare-Ups: A Retrospective Cohort Study in Taiwan.

Thromboembolism (TE) notably increase morbidity and mortality among inflammatory bowel disease (IBD) patients. Despite ECCO's 2024 guidelines advocating routine anticoagulant prophylaxis, its application in Asia remains inconsistent due to a lack of regional studies. This research investigates the incidence and predictors of TE during IBD-related hospitalizations in Taiwan, aiming to improve prevention strategies. Our retrospective cohort study included 282 adult IBD patients, accounting for 515 flare-up related hospitalizations at Linkou Chang Gung Memorial Hospital from January 2001 to March 2024. Patients were classified into two groups based on the occurrence of TE. The incidence of TE was 1.55%. The TE group had significantly lower body weight, body mass index (BMI), hemoglobin and albumin levels but higher rate of sepsis and concurrent autoimmune diseases compared to the non-TE group. Multivariate analysis indicated that concurrent autoimmune diseases and hypoalbuminemia were independent predictors of TE. The optimal serum albumin cutoff was established at 3.01 g/dL, with sensitivities and specificities of 87.5% and 77.3%, respectively. This pioneering Asian study identifies concurrent autoimmune diseases and low serum albumin as key predictors of TE in hospitalized IBD patients. We recommend targeted anticoagulant prophylaxis for IBD patients with these risk factors, especially when serum albumin falls below 3.01 g/dL.

Utilization of endovascular thrombectomy in patients with antiphospholipid syndrome and acute ischemic stroke

Abstract Background Antiphospholipid syndrome (APS) is a prothrombotic state and can cause acute ischemic stroke (AIS) particularly in younger individuals. Purpose Given the recent widespread adoption of endovascular thrombectomy (EVT) in patients with AIS, we aimed to evaluate the current trends and utilization of this technique in patients with APS. Methods We used National Readmission Database (NRD) to identify patients admitted between 2016 and 2020 with a primary diagnosis of AIS and a concurrent diagnosis of APS using relevant ICD-10 CM codes. Results Our analysis identified a total of 2,535,777 patients admitted for AIS, of which 7209 had a concomitant diagnosis of APS. The median age in patients with APS was 55 compared to 71 in non-APS patients (p < 0.001). APS patients also exhibited a lower prevalence of comorbidities such as coronary artery disease (4% vs. 28%; p < 0.001), congestive heart failure (CHF) (15% vs. 19%; p < 0.001), atrial fibrillation (14% vs. 26%), and diabetes (12% vs. 18%; p < 0.001). Systemic lupus erythematosus (SLE) was the most prevalent concurrent autoimmune disease in the APS cohort (19%). Patients with APS were significantly more likely to undergo EVT compared to their non-APS counterparts (5.2% vs. 3.5%; p < 0.001). Mortality was higher in non-APS likely due to older age compared to non-APS but didn’t reach statistical significance (4.4% vs 3.7%, p=0.070). Notably, the length of hospital stay was significantly higher for patients with APS (median: 6 days) compared to the non-APS group (median: 3 days; p < 0.001). Furthermore, we observed a steady increase in the utilization of EVT in patients with APS and AIS from 2016 (3.7%) to 2020 (6.8%; p = 0.02). Conclusion Our findings demonstrate that patients with AIS and concurrent APS are more likely to undergo endovascular thrombectomy, potentially due to a higher stroke burden. Additionally, the study revealed a progressive increase in the use of EVT for this specific patient population.

National Registry for Childhood Onset Scleroderma I: Insights from the first 341 juvenile localized scleroderma patients.

There is an under recognition of juvenile-onset localized scleroderma and its extracutaneous manifestations leading to delay in systemic treatment. Our study aims to address this gap by describing the demographics, presentation, associated family history, concurrent autoimmune disease, extracutaneous manifestations, laboratory evaluation, treatment, and course of disease in juvenile-onset localized scleroderma patients enrolled in the National Registry for Childhood Onset Scleroderma. Participants for this study were derived from the National Registry for Childhood Onset Scleroderma and included 341 patients with juvenile-onset localized scleroderma. Demographic, and prospectively collected outcome measures, such as the Localized Scleroderma Cutaneous Assessment Tool, physical exam findings, laboratory values, and patient-reported outcomes were reviewed. Most patients were female (71%), Caucasian (94%), had a linear subtype (56%), and had the onset of disease at age 7.5 (±4.2) years, and diagnosis 1.9 (±2.6) years after symptom onset. Most patients experienced at least one extracutaneous manifestation (70%), most commonly musculoskeletal (57%), followed by neurological (46%), and ophthalmological (11%). Those with musculoskeletal extracutaneous manifestation have significantly abnormal inflammatory and antibody laboratory values. Of patients with 1-year follow-up, a majority were treated with systemic therapy and globally improved with significant reduction in both modified Localized Scleroderma Skin Index (p < 0.001) and Localized Scleroderma Damage Index (p = 0.001). The study highlights need for earlier recognition of juvenile-onset localized scleroderma after demonstrating the delay in diagnosis and frequent extracutaneous manifestations with significant disease burden in a juvenile-onset localized scleroderma cohort. The benefits of systemic treatment and full extracutaneous manifestation screening in juvenile-onset localized scleroderma is supported.

Association of anti-Ro-52 antibodies with occurrence of interstitial lung disease in patients with idiopathic inflammatory myopathy

BackgroundAnti-Ro-52 antibodies have been associated with interstitial lung disease (ILD) in various autoimmune diseases. However, their role in ILD among patients with idiopathic inflammatory myopathies (IIMs) is relatively underexplored. This study aimed to investigate the association between anti-Ro-52 antibodies and the occurrence of ILD in individuals with IIMs.MethodsThis retrospective observational study included 604 patients who underwent myositis autoantibody testing between July 2018 and January 2021 at our hospital and were diagnosed with either IIMs or IIM-mimics. Comparative analyses were conducted between IIMs and IIM-mimics, as well as within the IIM group between cases with and without ILD. Logistic regression or Firth’s logistic regression analyses were employed to assess the risk of ILD development in different IIM subgroups and myositis antibody categories.ResultsThis study included 190 patients with IIM and 414 patients with IIM-mimics. Patients with IIM demonstrated higher incidence of ILD, concurrent autoimmune disease, and a greater likelihood of various myositis autoantibodies when compared to the IIM-mimics group. Within the IIM patient cohort, those with ILD exhibited a later age of onset of IIM, an increased mortality rate, and a more frequent presence of anti-aminoacyl-tRNA synthetase (ARS) antibodies compared to those without ILD. The presence of any myositis-specific antibody (MSA) was associated with a six-fold increased risk of ILD, while dual positivity for MSA and anti-Ro-52 antibodies conferred a twenty-fold risk. Anti-ARS antibodies carried a 14-fold increased risk of ILD, which escalated to 38-fold in cases of dual positivity for anti-ARS and anti-Ro-52 antibodies. Anti-Ro-52 antibodies alone increased the risk eight-fold.ConclusionsAmong patients with IIM, the presence of ILD was linked to higher mortality. Certain autoantibodies, notably anti-ARS and anti-Ro-52 antibodies, were associated with an increased risk of ILD. The greatest risk of ILD was observed in cases of dual positivity for anti-ARS and anti-Ro-52 antibodies.

Prevalence of autoimmune diseases in functional neurological disorder: influence of psychiatric comorbidities and biological sex

BackgroundFunctional neurological disorder (FND) is a common and disabling neuropsychiatric condition, which disproportionally affects women compared with men. While the etiopathogenesis of this disorder remains elusive, immune dysregulation is emerging...

Concurrent autoimmune blistering diseases in VEXAS syndrome: a report of two cases.

VEXAS (vacuoles, E1-enzyme, X-linked, autoinflammatory, somatic) syndrome is a recently characterized autoinflammatory condition driven by myeloid cell dysregulation. We report two patients with concurrent diagnoses of VEXAS syndrome and autoimmune blistering diseases – pemphigus vulgaris and dermatitis herpetiformis – highlighting a previously undescribed association between innate immune dysregulation and autoantibody-mediated skin diseases.

Prevalence of latent and overt polyautoimmunity in type 1 diabetes: A systematic review and meta-analysis

BackgroundPatients afflicted by type 1 diabetes (T1D) exhibit polyautoimmunity (PolyA). However, the frequency and distribution of PolyA in T1D is still unknown. ObjectiveWe conducted a systematic review and meta-analysis to define the prevalence of latent and overt PolyA in individuals with T1D. MethodsFollowing PRISMA guidelines, a comprehensive search across medical databases identified studies on latent and overt PolyA in T1D. Two researchers independently screened, extracted data, and assessed study quality. A random effects model was utilized to calculate the pooled prevalence, along with its corresponding 95 % confidence interval (CI), for latent PolyA and overt PolyA. Meta-regression analysis was conducted to study the effect of study designs, age, sex, and duration of disease on pooled prevalence. ResultsA total of 158 articles, encompassing a diverse composition of study designs were scrutinized. The analysis included 270,890 individuals with a confirmed diagnosis of T1D. The gender was evenly distributed (50.30 % male). Notably, our analysis unveiled an overt PolyA prevalence rate of 8.50 % (95 % CI, 6.77 to 10.62), with North America having the highest rates (14.50 %, 95 % CI, 7.58 to 24.89). This PolyA profile was further characterized by a substantial incidence of concurrent autoimmune thyroid disease (7.44 %, 95 % CI, 5.65 to 9.74). Moreover, we identified a notable prevalence of latent PolyA in the T1D population, quantified at 14.45 % (95 % CI, 11.17 to 18.49) being most frequent in Asia (23.29 %, 95 % CI, 16.29 to 32.15) and Oceania (21.53 %, 95 % CI, 16.48 to 27.62). Remarkably, this latent PolyA phenomenon primarily featured an array of autoantibodies, including rheumatoid factor, followed by Ro52, thyroid peroxidase antibodies, and thyroglobulin antibodies. Duration of the disease was associated with a highest frequency of latent (β: 0.0456, P-value: 0.0140) and overt PolyA (β: 0.0373, P-value: 0.0152). No difference in the pooled prevalence by study design was observed. ConclusionThis meta-analysis constitutes a substantial advancement in the realm of early detection of PolyA in the context of T1D. Individuals with T1D should regularly undergo assessments to identify potential concurrent autoimmune diseases, especially as they age.

Celiac disease prevalence in patients with idiopathic inflammatory myopathies, a cross-sectional study.

Up to 30% of patients with celiac disease (CD) suffer from concurrent autoimmune disease, compared to 3% of the general population. The association between CD and the current clinical phenotypes of inflammatory myopathies (IIM) patients has not been thoroughly addressed. Assess the CD features among patients with IIM and their relationship with the clinical phenotype and the myositis specific (MSA) and associated antibodies (MAA). For this cross-sectional study, we recruited 99 adult patients classified as IIM from a tertiary center in Mexico. We assessed serum MSA, MAA, and CD-associated autoantibodies (IgA anti-tissue transglutaminase (tTG) and both IgA and IgG anti-deaminated gliadin peptide (DGP)). Patients with highly suggestive serology for CD were then tested for IgG anti-endomysium antibodies, and a duodenal biopsy was performed. 70.7% of patients were positive for at least one antibody. Nine duodenal biopsies were taken, revealing findings compatible with celiac disease in two cases. Subjects with anti-MDA5 antibodies were more likely to have positive anti-tTG IgA antibodies (OR 6.76, 95% CI 1.85-24.62, P = 0.013) and suggestive CD serology (OR 6.41, 95% CI 1.62-25.29, P = 0.009). Patients with anti-Mi2 antibodies were more likely to have positive anti-DGP IgG antibodies (OR 3.35, 95% CI 1.12-9.96, P = 0.039), while positivity for these autoantibodies was less frequent in patients with anti-NXP2 antibodies (OR 0.22, 95% CI 0.06-0.80, P = 0.035). There is a higher prevalence of serologic and definite CD in patients with IIM compared to the general population. Identifying this subgroup of patients may have prognostic and therapeutic implications. Key points • The study estimated a serological celiac disease (CD) prevalence of 70.7% in patients with idiopathic inflammatory myopathies (IIM) and a biopsy-confirmed prevalence of 2%, suggesting that IIM patients should be considered a high-risk population for CD. • We identified a significant association between serological CD and the presence of anti-MDA5 and anti-Mi2 antibodies, suggesting a potential justification for celiac disease screening in this specific subgroup of patients. • The impact of gluten-free diets on IIM patients with serological markers of CD remains untested and warrants further investigation through prospective, randomized studies.

Graves’ disease and the risk of five autoimmune diseases: A Mendelian randomization and colocalization study

BackgroundEpidemiological studies have consistently demonstrated a high prevalence of concurrent autoimmune diseases in individuals with Graves' disease (GD). ObjectiveThe objective of this study is to establish a causal association between GD and autoimmune diseases. MethodsWe employed a two-sample Mendelian randomization (MR) to infer a causal association between GD and five autoimmune diseases, namely rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), Crohn's disease (CD), ulcerative colitis (UC), and amyotrophic lateral sclerosis (ALS), in the East Asian and European population. Genetic correlations were explored through linkage disequilibrium score regression analysis (LDSC). Finally, colocalization analyses were performed to investigate possible genetic foundations. ResultsBidirectional MR analysis indicated that genetically predicted GD increased the risk of RA (Odds Ratio (OR): 1.34, 95 % Confidence Interval (CI): 1.21 to 1.47, P < 0.001) and SLE (OR: 1.21, 95%CI: 1.08 to 1.35, P < 0.001) in the East Asian population. In contrast, we found that genetically predicted RA (OR: 1.14, 95%CI: 1.05 to 1.24, P = 0.002) and SLE (OR: 1.10, 95%CI: 1.03 to 1.17, P = 0.003) were associated with a higher risk of GD. The results have been partially validated in European cohorts. Colocalization analysis suggested the potential existence of shared causal variants between GD and other autoimmune diseases. In particular, gene ARID5B may play an important role in the incidence of autoimmune diseases. ConclusionThis study has confirmed that GD was associated with RA and SLE and found a possible key gene ARID5B. It may be necessary to strengthen detection to prevent the occurrence of comorbidities in clinical practice.

Occurrence and Risk Factors of Relapse Activity after Vaccination against COVID-19 in People with Multiple Sclerosis: 1-Year Follow-Up Results from a Nationwide Longitudinal Observational Study.

Several studies reported post-SARS-CoV-2-vaccination (PV) symptoms. Even people with multiple sclerosis (PwMS) have concerns about disease activity following the SARS-CoV-2 vaccination. We aimed to determine the proportion of PwMS with PV relapses, the PV annualized relapse rate (ARR), the time from vaccination to subsequent relapses, and identify sociodemographic/clinical risk factors for PV relapses. PwMS were surveyed several times at baseline and four follow-ups as part of a longitudinal observational study regarding the safety and tolerability of the SARS-CoV-2 vaccination. The inclusion criteria for this analysis were age ≥18 years, ≥1 SARS-CoV-2 vaccination, and ≥1-year observation period since initial vaccination. Of 2466 PwMS, 13.8% reported PV relapses (mostly after second [N = 147] or booster vaccination [N = 145]) at a median of 8.0 (first/third quantile: 3.55/18.1) weeks PV, with the shortest period following initial vaccination (3.95 weeks). The ARR was 0.153 (95% confidence interval: 0.138-0.168), with a median observation period since initial vaccination of 1.2 years. Risk factors for PV relapses were younger age, female gender, moderate-severe disability levels, concurrent autoimmune diseases, relapsing-remitting MS courses, no DMT, and relapses within the year prior to the first vaccination. Patients' health conditions before/during initial vaccination may play a more important role in PV relapse occurrence than vaccination per se.

Predictive value of the systemic immune inflammation index and systemic inflammatory response index on omalizumab drug survival in chronic spontaneous urticaria

Abstract Background Omalizumab is recommended as adjunctive therapy for antihistamine-refractory chronic spontaneous urticaria (CSU). However, its long-term effectiveness is understudied. The systemic immune-inflammation index (SII) and the systemic inflammatory response index (SIRI) have shown prognostic value in cancer, strokes, and other diseases. Objectives This study aimed to evaluate the long-term effectiveness of omalizumab in CSU patients while investigating potential associations of SII and SIRI with the drug survival of omalizumab. Methods A retrospective study was conducted using patient data from the electronic hospital database, including patients with CSU treated with omalizumab between January 2018 and May 2021. Drug survival curves were visualized using Kaplan-Meier survival analysis. and Cox regression was utilized to assess potential associations. Results A total of 109 CSU treated with omalizumab at the University Hospital of Zurich were included. The mean drug survival was 13.6 ± 10.9 months. The mean SII and SIRI were 796.1 ± 961.3 and 2.1 ± 3.1, respectively. The multivariate model revealed that SIRI (p = 0.098) was a more robust predictor of omalizumab’s drug survival than SII (p = 0.367), while concurrent autoimmune disease or baseline immunoglobulin E (IgE) levels showed no significant impact. Conclusion This study suggests the potential utility of SIRI as a superior predictive indicator for omalizumab’s drug survival in CSU patients compared to SII. Concomitant autoimmune disease or baseline IgE levels did not significantly affect the drug’s effectiveness.

Association of Autoimmune Diseases and Their Effect on Outcomes of Heparin-Induced Thrombocytopenia: An Analysis of the National Inpatient Sample (2016-2020)

Introduction: Heparin-Induced Thrombocytopenia (HIT) is a prothrombotic reaction to heparin exposure caused by antibodies directed towards heparin-platelet protein platelet factor 4 complexes. This thrombocytopenia is associated with and can lead to fatal venous and arterial thrombosis. This study aims to compare outcomes and assess the association of autoimmune diseases with HIT. Methods: A query of the National Inpatient Sample (2016-2020) was performed for index admissions with a principal diagnosis of HIT and concurrent autoimmune diseases using ICD 10 codes. Patient demographics and outcomes were identified. Univariate analysis with t-test or chi-squared was performed where appropriate. A multivariate regression analysis was used to generate adjusted odds ratios (AOR), adjusting for age, race, sex, and Charlson Comorbidity Index (CCI) score. The P-value significance was set at &amp;lt;0.05. All analysis was performed in STATA MP version 14.2. Results: A total of 72,935 patients with HIT met the inclusion criteria, of which, 2.88% had an underlying autoimmune disease. Those with auto-immune disease had a greater proportion of Caucasians, females, and younger patients. While there were no statistically significant differences in mortality, embolic, or bleeding events, patients with autoimmune disease were 43% less likely to become septic (AOR 0.57, p-value 0.006). Additionally, patients with autoimmune diseases had a lower mean hospital services charge and length of stay (p&amp;lt;0.001). Conclusion: Patients with HIT and autoimmune disease showed better outcomes in terms of sepsis, mean length of stay, and hospital services charge without any significant difference in embolic or bleeding outcomes. Underlying autoimmune disease likely does not confer any additional risk to HIT hospitalizations. This might be speculated to be due to the different underlying pathology driving HIT or accompanying immunosuppressants treatment in autoimmune diseases hindering the aggressiveness of immune response.

Lymphoma Treatment Alterations in the Context of Autoimmune Disease

Background: Autoimmune disease (AD) confers an increased risk for lymphoma. Several studies have shown that pre-existing AD portends a worse prognosis for lymphoma patients, but the reasons for this are unknown. 1,2,3 We hypothesize that one reason may be poor treatment tolerance in AD patients due to concurrent risk for cytopenias, infections, and immune-related adverse events. Methods: We conducted a retrospective cohort study to understand whether AD is associated with higher risk for treatment alterations, hospitalizations, and transfusions among lymphoma patients. The study population consisted of adult patients (aged 18-74 at lymphoma diagnosis) who underwent lymphoma treatment at one tertiary care center from 2017-2022. Patients who developed AD after or within the 12 months before lymphoma diagnosis were excluded to avoid including patients whose AD was paraneoplastic or a treatment side effect. Subjects were found by using cohort builder in electronic medical record then reviewing records for eligibility. The primary exposure of interest was pre-existing diagnosis of AD and the primary outcome was treatment alteration, such as dose reduction, delay, or discontinuation. The secondary outcomes were hospitalization, and transfusion. Outcomes were compared between groups with non-parametric tests. Logistic regression was used to estimate the association of AD with any treatment alteration. Results: We reviewed 357 records, with 30 eligible for inclusion in AD cohort and 65 eligible for non-AD cohort. There were 17 different lymphoma types with diffuse large B cell lymphoma as the most common (10 in AD cohort, 20 in non-AD). In the AD cohort, there were 12 distinct autoimmune diagnoses and rheumatoid arthritis was the most common (n=11). Baseline patient characteristics did not differ between the AD and non-AD cohorts in age, sex, diagnosis, stage, renal function, hemoglobin or type of treatment received. However, patients in the AD cohort were more likely to be Black or Asian compared to the non-AD cohort (Table 1). There were no differences in frequency of treatment alterations, unplanned hospitalizations, or incidence of transfusion between the AD and non-AD groups. Logistic regression showed no association of study group with incidence of any treatment alteration, even after controlling for baseline characteristics. Discussion: This study examines whether autoimmune disease impacts treatment tolerance among lymphoma patients. In a Swedish retrospective study of lymphoma, worse outcomes were seen among patients with AD due to increased non-lymphoma risk of death, suggesting that AD patients may have more frequent serious and life-threatening complications from lymphoma therapy. 1 In our study, there were no differences in treatment tolerance between the AD and non-AD groups. However, sample size is a limitation, and chart review is ongoing. Notably, treatment alterations were common in both groups, and no increase in unplanned hospitalizations was seen in the AD group. Clinical decisions to dose reduce, delay or discontinue therapy may mitigate against hospitalization from serious treatment related complications even in lymphoma patients with concurrent AD. Future directions include examining interactions between treatment alterations, autoimmune disease, and prognosis in specific lymphoma subtypes. 1. Simard JF, Baecklund F, Chang ET, Baecklund E, Hjalgrim H, et al. Lifestyle factors, autoimmune disease and family history in prognosis of non-hodgkin lymphoma overall and subtypes. Int J Cancer. 2013 Jun 1;132(11):2659-66. doi: 10.1002/ijc.27944. Epub 2012 Dec 3. PMID: 23160780. 2. Jachiet V, Mekinian A, Carrat F, Grignano E, Retbi A, Boffa JJ, et al. Autoimmune manifestations associated with lymphoma: Characteristics and outcome in a multicenter retrospective cohort study. Leuk. Lymphoma. 2018;59:1399-1405 3. Kleinstern G, Averbuch M, Abu Seir R, Perlman R, Ben Yehuda D, Paltiel O. Presence of autoimmune disease affects not only risk but also survival in patients with B-cell non-Hodgkin lymphoma. Hematol. Oncol. 2018;36:457-462.

Association Vs Causation: Epidemiologic Clues As to the Autoimmune Pathogenesis of MDS

Multiple clinical associations of MDS and autoimmunity have been described, but the pathogenesis and cause-effect relationship are likely diverse and possibly intertwining. Telomeropathies, while increasing risk of bone marrow failure, can be also associated with liver or lung fibrosis and therapies for Wegener's granulomatosis can predispose to MDS. Moreover, clonal hematopoiesis (CH) seems to be more prevalent in some autoimmune diseases 1 (AD) perpetuating a process that may ultimately lead to increased risk of MDS. Reverse scenarios are also possible and AD can be a result of MDS as a form of paraneoplastic syndrome. The recently established relationship of somatic UBA1 mutations and MDS with autoimmune manifestations exemplifies such a scenario e.g., VEXAS syndrome 2. This remarkable configuration prompted us to systematically investigate the relationships between autoimmune symptomatology and MDS including genomic features such as UBA1 mutations, pathomorphological phenotypes, and demographics. We have investigated 1,903 MDS patients for the presence and the anamnestic evidence of AD. A total of 197 patients (about 10%) had a concurrent well-defined AD (5.3%) or positive inflammatory/autoimmune markers (4.9%; fibromyalgia and chronic fatigue syndrome invoked 0.3% of MDS cases and were not counted). Of those, polymyalgia rheumatica, systemic lupus erythematosus and rheumatoid arthritis were most common accounting for 13%, 5.5% and 19% of MDS cases with autoimmunity. The remaining 60% involved the presence of serological markers such as ANA, anti-RNP and anti-SSA among others (45%, 4%, 2%, respectively) without fulfilling the criteria for specific autoimmune entities. The gender distribution of cases with MDS/autoimmune features was similar to the general MDS demographics and cases without autoimmune conditions. A similar distribution was seen among males and females in both groups, with males representing 84% of each subgroup and females accounting for 16%. When stratified by risk criteria, 58% of patients with MDS/AD were found to have low risk disease (&amp;lt;5% of blasts) compared to patients without AD (46%; p= .74), while intermediate to high risk (HR) categories were seen in 42% and 52% (p= .74), respectively. While trisomy 8 and complex karyotype were underrepresented in MDS with AD (15% vs 22%, 4.5% vs 10%), del(11q), del(12q) and del(20q) were more common among patients with AD (10% vs 5.8%). When we screened the genomic landscape of AD/MDS, we found more mutations in TET2 (24 vs 13%, p= .004), SF3B1 (14 vs 8%, p= .026), BCORL1 (5 vs 1.5%, p= .026), DNMT3A (13 vs 6%, p= .003), IDH1 (3 vs 0.8%, p= .01), and CEBPA (3 vs 0.8%, p= .04) compared to patients without AD ( Fig.1) With a median follow up of 19 months, female patients with AD showed better 1-year survival rate of 89% vs 65% in cases without AD, (p= .044). A similar trend was seen for transformation to AML. However, such differences were not found among males. Next, we determined the etiologic fraction of the MDS/AD clinical dyad explained by the presence of VEXAS by screening UBA1 mutation in our cohort. We found mutations in 0.5% of MDS/AD vs 0.05% of the total cohort (p=0.1). To further expand on MDS association with AD, we investigated other potential autoimmune syndromes and found 0.5% of MDS with co-associated LGL with 1/3 of them presenting with RA. Notably, in the hypocellular MDS subgroup (n=175), 9.7% had concomitant AD (p= .89). Similarly, 0.3% of evaluable patients had Sweet syndrome, of which 16% associated with autoimmune conditions. Finally, since AD appear to be frequent in MDS, we queried whether in our internal cohort of CHIP patients (n=115), their prevalence could be analogous. Indeed, AD were present in a fraction similar to that of manifest MDS (around 5%). Moreover, in all of these patients, similar to those with MDS, the autoimmune diagnosis preceded that of CHIP with the caveat that, unlike MDS, CHIP may have evolved much sooner than the original diagnosis but was not screened. Our study provides valuable insights into the intricate relationship between MDS and AD. Our findings demonstrate that MDS and autoimmunity are linked through diverse mechanisms, with potential cause-effect relationships existing in both directions. Figure 1. Frequency of mutations Graph shows frequency of mutations among patients with autoimmune diseases (AD) in MDS versus those without AD.* p&amp;lt;0.05, **p&amp;lt;0.001.

Clinical and molecular impact of concurrent thyroid autoimmune disease and thyroid cancer: From the bench to bedside.

The recent incorporation of immune checkpoint inhibitors targeting the PD-1 (programmed cell death receptor 1) and CTLA-4 (cytotoxic T lymphocyte antigen 4) pathways into the therapeutic armamentarium of cancer has increased the need to understand the correlation between the immune system, autoimmunity, and malignant neoplasms. Both autoimmune thyroid diseases and thyroid cancer are common clinical conditions. The molecular pathology of autoimmune thyroid diseases is characterized by the important impact of the PD-1/PD-L1 axis, an important inhibitory pathway involved in the regulation of T-cell responses. Insufficient inhibitory pathways may prone the thyroid tissue to a self-destructive immune response that leads to hypothyroidism. On the other hand, the PD-1/PD-L1 axis and other co-inhibitory pathways are the cornerstones of the immune escape mechanisms in thyroid cancer, which is a mechanism through which the immune response fails to recognize and eradicate thyroid tumor cells. This common mechanism raises the idea that thyroid autoimmunity and thyroid cancer may be opposite sides of the same coin, meaning that both conditions share similar molecular signatures. When associated with thyroid autoimmunity, thyroid cancer may have a less aggressive presentation, even though the molecular explanation of this clinical consequence is unclear. More studies are warranted to elucidate the molecular link between thyroid autoimmune disease and thyroid cancer. The prognostic impact that thyroid autoimmune disease, especially chronic lymphocytic thyroiditis, may exert on thyroid cancer raises important insights that can help physicians to better individualize the management of patients with thyroid cancer.

CD19-targeted chimeric antigen receptor T-cell therapy in patients with concurrent B-cell Non-Hodgkin lymphoma and rheumatic autoimmune diseases: a propensity score matching study.

Rheumatic autoimmune diseases not only involve the production of autoantibodies but also demonstrate T-cell dysfunction. In patients with concurrent B-cell non-Hodgkin lymphoma (NHL) and rheumatic autoimmune diseases, the safety and efficacy of CD19-targeted chimeric antigen receptor (CAR) T-cell therapy are unknown. Using an aggregated electronic health record database, patients with rheumatic autoimmune diseases (auto group) were compared to propensity score-matched patients without rheumatic autoimmune diseases (non-auto group). From 1/2019 to 1/2023, 58 (4.3%) of 1,363 patients who received CD19-targeted CAR T-cell therapy had concurrent rheumatic autoimmune diseases. Both groups had similar incidence, severity, and management of cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). Moreover, the two groups had similar time-to-next treatment or death (hazard ratio [HR] 0.97, 95% confidence interval [CI] 0.60 to 1.59, log-rank p = 0.91) and overall survival (HR 0.90, 95%CI 0.46 to 1.78, p = 0.76). Following CAR T-cell infusion, patients with rheumatic autoimmune diseases achieved decreased inflammatory markers, seronegative conversion of autoantibodies, as well as reduced use of steroids and disease-modifying anti-rheumatic drugs. In conclusion, the safety and efficacy of CAR T-cell therapy were not affected in patients with rheumatic autoimmune diseases. Moreover, they achieved better biochemical control of underlying rheumatic diseases.

Esophagogastric Junction Outflow Obstruction Is Likely to Be a Local Manifestation of Other Primary Diseases: Analysis of Single-Center 4-Year Follow-Up Data.

Whether esophagogastric junction outflow obstruction (EGJOO) is a variant of achalasia cardia (AC) or an esophageal motility state of certain organic or systemic diseases remains controversial. We aimed to investigate the differences between EGJOO and AC in clinical characteristics and outcomes through a 4-year follow-up. Patients diagnosed with primary EGJOO or AC were included. Based on the presence of concomitant disease, EGJOO patients were divided into a functional and an anatomical EGJOO group; similarly, patients with AC were divided into an AC with organic disease group and a true AC group. Disease characteristics and high-resolution manometry (HRM) parameters were retrospectively compared between the groups, and the development of organic diseases that could affect esophageal motility disorders and responses to treatment were examined during the follow-up. Symptom relief was defined as an Eckardt score of ≤3 after the treatment. The study included 79 AC patients and 70 EGJOO patients. Compared with patients with AC, EGJOO patients were older, had shorter disease duration, a lower Eckardt score, and were more likely to have concurrent adenocarcinoma of the esophagogastric junction (AEG) and autoimmune disease (p < 0.05 for all). The severity of dysphagia and Eckardt scores were higher in the anatomical EGJOO group than in the functional EGJOO group. Significant differences were seen in HRM parameters (UES residual pressure, LES basal pressure, and LES residual pressure) between AC and EGJOO patients. However, no significant differences in HRM parameters were observed between the functional EGJOO and anatomical EGJOO groups. Sixty-seven (95.71%) patients with EGJOO and sixty-nine (87.34%) patients with AC experienced symptom relief (p = 0.071). Among patients achieving symptom relief, a relatively large proportion of patients with EGJOO had symptom relief after medications (37/67, 55.22%), the resolution of potential reasons (7/67, 10.45%), and spontaneous relief (15/67, 22.39%), while more patients with AC had symptom relief after POEM (66/69, 95.65%). Among EGJOO patients achieving symptom relief, more patients (7/20, 35%) with anatomical EGJOO had symptom relief after the resolution of potential reasons for EGJOO, while more patients (32/47, 68.09%) with functional EGJOO had symptom relief with medications. Concurrent AEG and autoimmune diseases are more likely in EGJOO than in AC. A considerable part of EGJOO may be the early manifestation of an organic disease. Anatomical EGJOO patients experience symptom improvement with the resolution of primary diseases, while most functional EGJOO patients experience symptom relief with pharmacotherapy alone or even without any treatment.

Incidence and predictors of infections in patients with advanced non-small cell lung cancer treated with checkpoint inhibitor immunotherapies: A monocentric retrospective cohort study.

Immune checkpoint inhibitors (ICIs) represent the cornerstone of the current treatment of non-small cell lung cancer (NSCLC). However, the occurrence of concomitant infections might hamper success. All consecutive patients with advanced NSCLC who started ICIs as a first- or second-line therapy from January 1, 2017 to June 30, 2020 were retrospectively evaluated. The occurrence of infectious events during ICIs was correlated with clinical characteristics, including previous Cytotoxic Chemotherapy (CC), occurrence of immune-related-adverse-events (irAEs). A total of 211 patients were included, 46 (22%) females, with a median (q1-q3) age of 69 (62-76) years. Overall, 85 patients (40%) received ICIs as a first treatment line and 126 (60%) as a second line; 40 patients (19%) had at least one infection during ICIs, and 17 (8%) more than one. Notably, autoimmune diseases (P < .005), neutropenia (P = .001) or infections during previous CC (P = .001), irAEs (P = .006), or steroid therapy for irAEs (P < .001) were associated with infection development. By multivariate Cox-regression, autoimmune diseases (aHR = 6.27; 95%CI = 2.38-16.48; P < .001) and steroid therapy for irAEs (aHR = 2.65; 95%CI = 1.27-5.52; P < .009) were associated with a higher risk of infection during ICIs. Interestingly, autoimmune diseases were confirmed as risk factors in patients treated with ICIs as a first line, while previous infections were the only independent predictor of infections in patients treated with ICIs as a second line. Patients with NSCLC treated with ICIs with concurrent autoimmune disease, receiving steroid therapy for management of irAEs, or having a history of previous infections during CC should be actively monitored for the risk of developing infectious complications.