Tag: autoimmune diseases

Incidence of immune-mediated inflammatory diseases following COVID-19: a matched cohort study in UK primary care

Abstract:

Background: Some patients infected with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) go on to experience post-COVID-19 condition or long COVID. Preliminary findings have given rise to the theory that long COVID may be due in part to a deranged immune response. In this study, we assess whether there is an association between SARS-CoV-2 infection and the incidence of immune-mediated inflammatory diseases (IMIDs).

Methods: Matched cohort study using primary care electronic health record data from the Clinical Practice Research Datalink Aurum database. The exposed cohort included 458,147 adults aged 18 years and older with a confirmed SARS-CoV-2 infection and no prior diagnosis of IMIDs. They were matched on age, sex, and general practice to 1,818,929 adults with no diagnosis of confirmed or suspected SARS-CoV-2 infection. The primary outcome was a composite of any of the following IMIDs: autoimmune thyroiditis, coeliac disease, inflammatory bowel disease (IBD), myasthenia gravis, pernicious anaemia, psoriasis, rheumatoid arthritis (RA), Sjogren’s syndrome, systemic lupus erythematosus (SLE), type 1 diabetes mellitus (T1DM), and vitiligo. The secondary outcomes were each of these conditions separately. Cox proportional hazard models were used to estimate adjusted hazard ratios (aHR) and 95% confidence intervals (CI) for the primary and secondary outcomes, adjusting for age, sex, ethnic group, smoking status, body mass index, relevant infections, and medications.

Results: Six hundred and nighty six (0.15%) and 2230 (0.12%) patients in the exposed and unexposed cohort developed an IMID during the follow-up period over 0.29 person-years, giving a crude incidence rate of 4.59 and 3.65 per 1000 person-years, respectively. Patients in the exposed cohort had a 22% increased risk of developing an IMID, compared to the unexposed cohort (aHR 1.22, 95% CI 1.12 to 1.33). The incidence of three IMIDs was significantly associated with SARS-CoV-2 infection. These were T1DM (aHR 1.56, 1.09 to 2.23), IBD (aHR 1.36, 1.18 to 1.56), and psoriasis (1.23, 1.05 to 1.42).

Conclusions: SARS-CoV-2 was associated with an increased incidence of IMIDs including T1DM, IBD and psoriasis. However, these findings could be potentially due to ascertainment bias. Further research is needed to replicate these findings in other populations and to measure autoantibody profiles in cohorts of individuals with COVID-19.

Source: Syed U, Subramanian A, Wraith DC, Lord JM, McGee K, Ghokale K, Nirantharakumar K, Haroon S. Incidence of immune-mediated inflammatory diseases following COVID-19: a matched cohort study in UK primary care. BMC Med. 2023 Sep 21;21(1):363. doi: 10.1186/s12916-023-03049-5. PMID: 37735654; PMCID: PMC10512476. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10512476/ (Full text)

Risk of autoimmune diseases in patients with COVID-19: A retrospective cohort study

Abstract:

Background: There are a growing number of case reports of various autoimmune diseases occurring after COVID-19, yet there is no large-scale population-based evidence to support this potential association. This study provides a closer insight into the association between COVID-19 and autoimmune diseases and reveals discrepancies across sex, age, and race of participants.

Methods: This is a retrospective cohort study based on the TriNetX U.S. Collaborative Network. In the test-negative design, cases were participants with positive polymerase chain reaction (PCR) test results for SARS-CoV-2, while controls were participants who tested negative and were not diagnosed with COVID-19 throughout the follow-up period. Patients with COVID-19 and controls were propensity score-matched (1: 1) for age, sex, race, adverse socioeconomic status, lifestyle-related variables, and comorbidities. The primary endpoint is the incidence of newly recorded autoimmune diseases. Adjusted hazard ratios (aHRs) and 95% confident intervals (CIs) of autoimmune diseases were calculated between propensity score-matched groups with the use of Cox proportional-hazards regression models.

Findings: Between January 1st, 2020 and December 31st, 2021, 3,814,479 participants were included in the study (888,463 cases and 2,926,016 controls). After matching, the COVID-19 cohort exhibited significantly higher risks of rheumatoid arthritis (aHR:2.98, 95% CI:2.78-3.20), ankylosing spondylitis (aHR:3.21, 95% CI:2.50-4.13), systemic lupus erythematosus (aHR:2.99, 95% CI:2.68-3.34), dermatopolymyositis (aHR:1.96, 95% CI:1.47-2.61), systemic sclerosis (aHR:2.58, 95% CI:2.02-3.28), Sjögren’s syndrome (aHR:2.62, 95% CI:2.29-3.00), mixed connective tissue disease (aHR:3.14, 95% CI:2.26-4.36), Behçet’s disease (aHR:2.32, 95% CI:1.38-3.89), polymyalgia rheumatica (aHR:2.90, 95% CI:2.36-3.57), vasculitis (aHR:1.96, 95% CI:1.74-2.20), psoriasis (aHR:2.91, 95% CI:2.67-3.17), inflammatory bowel disease (aHR:1.78, 95%CI:1.72-1.84), celiac disease (aHR:2.68, 95% CI:2.51-2.85), type 1 diabetes mellitus (aHR:2.68, 95%CI:2.51-2.85) and mortality (aHR:1.20, 95% CI:1.16-1.24).

Interpretation: COVID-19 is associated with a different degree of risk for various autoimmune diseases. Given the large sample size and relatively modest effects these findings should be replicated in an independent dataset. Further research is needed to better understand the underlying mechanisms.

Source: Chang R, Yen-Ting Chen T, Wang SI, Hung YM, Chen HY, Wei CJ. Risk of autoimmune diseases in patients with COVID-19: A retrospective cohort study. EClinicalMedicine. 2023 Feb;56:101783. doi: 10.1016/j.eclinm.2022.101783. Epub 2023 Jan 10. PMID: 36643619; PMCID: PMC9830133. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9830133/ (Full text)

Long COVID: an estrogen-associated autoimmune disease?

Introduction:

Some people who have had severe to a moderate or mild form of COVID-19 disease may suffer from variable and debilitating symptoms for many months after the initial infection. This condition is commonly called “Long COVID”. An exact definition is missing, but symptoms with a duration of more than 2 months are typically considered as Long COVID. The condition is characterized by long-term sequelae and can involve a range of symptoms such as persistent fatigue, headache, shortness of breath, anosmia, muscle weakness, fever, cognitive dysfunction (brain fog), tachycardia, intestinal disorders, and skin manifestations. Long COVID syndrome bears a similarity to the post-infectious syndromes that followed the outbreaks of chikungunya and Ebola.

In general, women appear to be twice as likely to develop Long COVID as men, but only until around age 60, when the risk level becomes similar. In addition to being a woman, older age and a higher body mass index also seem to be risk factors for having Long COVID.

Source: Ortona E, Buonsenso D, Carfi A, Malorni W; Long Covid Kids study group. Long COVID: an estrogen-associated autoimmune disease? Cell Death Discov. 2021 Apr 13;7(1):77. doi: 10.1038/s41420-021-00464-6. PMID: 33850105; PMCID: PMC8042352.  https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8042352/ (Full text)

Fatigue in ANCA-associated vasculitis (AAV) and systemic sclerosis (SSc): similarities with Myalgic encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS). A critical review of the literature

Abstract:

Introduction: Persistent debilitating fatigue is a frequent complaint in patients with systemic autoimmune rheumatic diseases (SARDs). Fatigue is, however, frequently overlooked in the clinic, and patients who successfully achieve remission of their disease, often still have a lowered quality of life due to its persistence. How similar is this fatigue to Myalgic encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS), what is this fatigue associated with, and what tools/approaches (if any), have resulted in the improvement of fatigue in these patients is poorly defined.

Areas covered: Similarities between the pathophysiology of ME/CFS, systemic sclerosis (SSc) and primary systemic vasculitides (PSV) are discussed, followed by an in-depth review of the prevalence and correlates of fatigue in these diseases. The authors reviewed literature from MEDLINE, APA PsycInfo, Embase, and CINAHL.

Expert opinion: Persistent fatigue is a prominent feature in SARDs and may not be associated with components commonly associated with disease activity and/or progression. Immune and metabolic commonalities exist between ME/CFS, SSc, and PSVs – suggesting that common pathways inherent to the diseases and fatigue may be present. We suggest that patients with features of ME/CFS need to be identified by treating physicians, as they may require alternative approaches to therapy to improve their quality of life.

Source: van Eeden C, Osman MS, Cohen Tervaert JW. Fatigue in ANCA-associated vasculitis (AAV) and systemic sclerosis (SSc): similarities with Myalgic encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS). A critical review of the literature. Expert Rev Clin Immunol. 2022 Aug 31:1-22. doi: 10.1080/1744666X.2022.2116002. Epub ahead of print. PMID: 36045606. https://pubmed.ncbi.nlm.nih.gov/36045606/

Increased risks of cancer and autoimmune disease among the first-degree relatives of patients with myalgic encephalomyelitis (ME)/chronic fatigue syndrome (CFS)

Background: Myalgic encephalomyelitis (ME)/chronic fatigue syndrome (CFS) is a disabling multi-system complex disorder with prevalence of 875 per 100,000 (up to 3.4 million people) in the United States. There are no known etiologic or risk factors and no approved treatments for ME/CFS. We conducted a molecular epidemiologic study to test the hypothesis that ME/CFS may be an autoimmune disease (AID) and explore the link between ME/CFS and cancer, specifically hematologic malignancies.Methods: Our clinic-based study involved carefully selected cases with confirmed diagnosis of ME/CFS (n=59) and healthy controls (n=54) frequency matched to cases on age, gender and ethnicity. During structured interviews, detailed multi-generation pedigrees, epidemiologic and medical questionnaires, and biospecimen were obtained on all subjects. Statistical analysis of pedigree data involved comparison of cases and controls with respect to the prevalence and cumulative incidence of AID and cancer among their first-degree relatives. For unadjusted analysis, risk ratios, 95% confidence intervals (CI), and p-values were calculated. For age-adjusted analyses, cumulative incidence estimates were compared using the log-rank test.

Results: The prevalence of AID was significantly higher among the first-degree relatives of cases compared to those of controls (OR=5.30; 95%CI: 1.83-15.38; p=0.001). The prevalence of AID among mothers was 14% for cases and 1.9% for controls (p=0.03). 11.2% of the first-degree relatives of cases had an AID compared to 3.1% of the relatives of controls (prevalence ratio=3.71; 95% CI: 1.74-7.88; p=0.0007). The cumulative incidence of AID among the first-degree relatives of ME/CFS cases was 9.4% compared to 2.7% for those of the controls (p=0.0025). First-degree relatives of ME/CFS cases had a significantly higher prevalence of any cancer compared to the relatives of unrelated controls (OR=4.06, 95%CI: 1.84-8.96, p=0.0005). Age-adjusted analysis revealed significantly higher (p=0.03) cumulative incidence of any cancer among the first-degree relatives of cases (20%) compared to the relatives of controls (15.4%). The cumulative incidence of hematologic cancers was also significantly higher among the relatives of cases (p<0.05).

Conclusions: We found statistically significant increased risks of AID and cancer among the first-degree relatives of ME/CFS cases. Our findings implicate immune dysregulation as an underlying mechanism, providing etiologic clues and leads for prevention. Given symptomatic similarities between ‘long COVID’ and ME/CFS, it is predicted that there will be a significant increase in incidence of ME/CFS as the result of COVID-19 pandemic. Our findings may enable defining a subset of COVID-19 patients who could be at risk of developing ME/CFS, and who may benefit from treatments used for certain AIDs.

Source: Roxana Moslehi, Anil Kumar, Amiran Dzutsev. Increased risks of cancer and autoimmune disease among the first-degree relatives of patients with myalgic encephalomyelitis (ME)/chronic fatigue syndrome (CFS) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 34. https://aacrjournals.org/cancerres/article/82/12_Supplement/34/700144

 

Carnitine Palmitoyl Transferase Deficiency in a University Immunology Practice

Abstract:

Purpose: This report describes the clinical manifestations of 35 patients sent to a University Immunology clinic with a diagnosis of fatigue and exercise intolerance who were identified to have low carnitine palmitoyl transferase activity on muscle biopsies.

Recent findings: All of the patients presented with fatigue and exercise intolerance and many had been diagnosed with fibromyalgia. Their symptoms responded to treatment of the metabolic disease. Associated symptoms included bloating, diarrhea, constipation, gastrointestinal reflux symptoms, recurrent infections, arthritis, dyspnea, dry eye, visual loss, and hearing loss. Associated medical conditions included Hashimoto thyroiditis, Sjogren’s syndrome, seronegative arthritis, food hypersensitivities, asthma, sleep apnea, and vasculitis. This study identifies clinical features that should alert physicians to the possibility of an underlying metabolic disease. Treatment of the metabolic disease leads to symptomatic improvement.

Source: Bax K, Isackson PJ, Moore M, Ambrus JL Jr. Carnitine Palmitoyl Transferase Deficiency in a University Immunology Practice. Curr Rheumatol Rep. 2020 Feb 14;22(3):8. doi: 10.1007/s11926-020-0879-9. PMID: 32067119. https://pubmed.ncbi.nlm.nih.gov/32067119/

Breast Implant-Associated Immunological Disorders

Abstract:

Background: Breast implants are commonly placed postbreast cancer reconstruction, cosmetic augmentation, and gender-affirming surgery. Breast implant illness (BII) is a systemic complication associated with breast implants. Patients with BII may experience autoimmune symptoms including fatigue, difficulty concentrating, hair loss, weight change, and depression. BII is poorly understood, and the etiology is unknown. The purpose of this literature review is to characterize BII autoimmune disorders and determine possible causes for its etiology.

Methods: The PubMed, Google Scholar, Embase, Web of Science, and OVID databases were interrogated from 2010 to 2020 using a query strategy including search term combinations of “implants,” “breast implant illness,” “autoimmune,” and “systemic illness.”

Results: BII includes a spectrum of autoimmune symptoms such as fatigue, myalgias/arthralgias, dry eyes/mouth, and rash. A review of epidemiological studies in the past ten years exhibited evidence affirming an association between breast implants and autoimmune diseases. The most commonly recognized were Sjogren’s syndrome, rheumatoid arthritis, systemic sclerosis, chronic fatigue syndrome, and Raynaud’s syndrome. Explantation resulted in alleviation of symptoms in over 50% of patients, strengthening the hypothesis linking breast implants to BII. Studies have shown that silicone is a biologically inert material and unlikely to be the cause of these symptoms. This is supported by the fact that increased risk of autoimmune disease was also reported in patients with other implantable biomaterials such as orthopedic implants. Recent studies shed light on a possible role of bacterial biofilm and subsequent host-pathogen interactions as a confounding factor to this problem.

Conclusion: BII could be dependent on biofilm infection and the microenvironment around the implants. The true pathophysiology behind these complaints must be further investigated so that alternative treatment regimens other than explantation can be developed. Translational significance of these studies is not limited to breast implants but extends to other implants as well.

Source: Suh LJ, Khan I, Kelley-Patteson C, Mohan G, Hassanein AH, Sinha M. Breast Implant-Associated Immunological Disorders. J Immunol Res. 2022 May 4;2022:8536149. doi: 10.1155/2022/8536149. PMID: 35571560; PMCID: PMC9095406. https://pubmed.ncbi.nlm.nih.gov/35571560/

A distinctive profile of family genetic risk scores in a Swedish national sample of cases of fibromyalgia, irritable bowel syndrome, and chronic fatigue syndrome compared to rheumatoid arthritis and major depression

Abstract:

Background: Functional somatic disorders (FSD) feature medical symptoms of unclear etiology. Attempts to clarify their origin have been hampered by a lack of rigorous research designs. We sought to clarify the etiology of the FSD by examining the genetic risk patterns for FSD and other related disorders.

Methods: This study was performed in 5 829 186 individuals from Swedish national registers. We quantified familial genetic risk for FSD, internalizing disorders, and somatic disorders in cases of chronic fatigue syndrome (CFS), fibromyalgia (FM), and irritable bowel syndrome (IBS), using a novel method based on aggregate risk in first to fifth degree relatives, adjusting for cohabitation. We compared these profiles with those of a prototypic internalizing psychiatric – major depression (MD) – and a somatic/autoimmune disorder: rheumatoid arthritis (RA).

Results: Patients with FM carry substantial genetic risks not only for FM, but also for pain syndromes and internalizing, autoimmune and sleep disorders. The genetic risk profiles for IBS and CFS are also widely distributed although with lower average risks. By contrast, genetic risk profiles of MD and RA are much more restricted to related conditions.

Conclusion: Patients with FM have a relatively unique family genetic risk score profile with elevated genetic risk across a range of disorders that differs markedly from the profiles of a classic autoimmune disorder (RA) and internalizing disorder (MD). A similar less marked pattern of genetic risks was seen for IBS and CFS. FSD arise from a distinctive pattern of genetic liability for a diversity of psychiatric, autoimmune, pain, sleep, and functional somatic disorders.

Source: Kendler KS, Rosmalen JGM, Ohlsson H, Sundquist J, Sundquist K. A distinctive profile of family genetic risk scores in a Swedish national sample of cases of fibromyalgia, irritable bowel syndrome, and chronic fatigue syndrome compared to rheumatoid arthritis and major depression. Psychol Med. 2022 Mar 31:1-8. doi: 10.1017/S0033291722000526. Epub ahead of print. PMID: 35354508.

Platelet Storage Pool Deficiency and Elevated Inflammatory Biomarkers Are Prevalent in Postural Orthostatic Tachycardia Syndrome

Abstract:

A significant number of postural orthostatic tachycardia syndrome (POTS) patients have platelet delta granule storage pool deficiency (δ-SPD).

The etiology of POTS is unknown but a number of laboratories, including ours, have reported elevations of G-protein-coupled adrenergic receptor and muscarinic acetylcholine receptor autoantibodies in POTS patients, detected by a variety of techniques, suggesting that the disorder is an autoimmune condition. Thus, it could also be considered an inflammatory disease.

In a pilot study, we investigated a limited number of platelet-related cytokines and chemokines and discovered many that were elevated.

This case–control study validates our pilot study results that POTS patients have an activated innate immune system.

Plasma of 35 POTS patients and 35 patients with unexplained bleeding symptoms and categorized as “non-POTS” subjects was analyzed by multiplex flow cytometry to quantify 16 different innate immune system cytokines and chemokines. Electron microscopy was used to quantify platelet dense granules.

Ten of 16 biomarkers of inflammation were elevated in plasma from POTS patients compared to non-POTS subjects, with most of the differences extremely significant, with p values < 0.0001.

Of particular interest were elevations of IL-1β and IL-18 and decreased or normal levels of type 1 interferons in POTS patients, suggesting that the etiology of POTS might be autoinflammatory.

All POTS patients had δ-SPD. With a growing body of evidence that POTS is an autoimmune disease and having elevations of the innate immune system, our results suggest a potential T-cell-mediated autoimmunity in POTS characteristic of a mixed-pattern inflammatory disease similar to rheumatoid arthritis.

Source: Gunning WT, Kramer PM, Cichocki JA, Karabin BL, Khuder SA, Grubb BP. Platelet Storage Pool Deficiency and Elevated Inflammatory Biomarkers Are Prevalent in Postural Orthostatic Tachycardia Syndrome. Cells. 2022; 11(5):774. https://doi.org/10.3390/cells11050774  https://www.mdpi.com/2073-4409/11/5/774/htm (Full text)

Undetected Jawbone Marrow Defects as Inflammatory and Degenerative Signaling Pathways: Chemokine RANTES/CCL5 as a Possible Link Between the Jawbone and Systemic Interactions?

Abstract:

Background: Cytokines, especially chemokines, are of increasing interest in immunology. This study characterizes the little-known phenomenon of “bone marrow defects of the jawbone” (BMDJ) with known overexpression of the chemokine RANTES/CCL5 (R/C).

Purpose: Our investigation clarifies why BMDJ and the intensity of local R/C overexpression are challenging to detect, as examined in patients with seven different systemic immunological diseases. Specifically, we investigate whether R/C overexpression is specific to certain disease groups or if it represents a type of signal disruption found in all systemic immunological diseases.

Patients and Methods: In a total of 301 patients, BMDJ was surgically repaired during clinical practice to reduce “silent inflammation” associated with the presence of jaw-related pathologies. In each case of BMDJ, bone density was measured preoperatively (in Hounsfield units [HU]), while R/C expression was measured postoperatively. Each of the 301 patients suffered from allergies, atypical facial and trigeminal pain, or were diagnosed with neurodegenerative diseases, tumors, rheumatism, chronic fatigue syndrome, or parasympathetic disorders.

Results: In all BMDJ cases, strongly negative HU values indicated decreased bone density or osteolysis. Consistently, all cases of BMDJ showed elevated R/C expression. These findings were consistently observed in every disease group.

Discussion: BMDJ was confirmed in all patients, as verified by the HU measurements and laboratory results related to R/C expression. The hypothesis that a specific subset of the seven disease groups could be distinguished either based on the increased presence of BMDJ and by the overexpression of R/C could not be confirmed. A brief literature review confirms the importance of R/C in the etiology of each of the seven disease groups.

Conclusion: In this research, the crucial role played by BMDJ and the chemokine R/C in inflammatory and immune diseases is discussed for seven groups of patients. Each specific immune disease can be influenced or propelled by BMDJ-derived R/C inflammatory signaling pathways.

Source: Lechner J, Schmidt M, von Baehr V, Schick F. Undetected Jawbone Marrow Defects as Inflammatory and Degenerative Signaling Pathways: Chemokine RANTES/CCL5 as a Possible Link Between the Jawbone and Systemic Interactions? J Inflamm Res. 2021 Apr 21;14:1603-1612. doi: 10.2147/JIR.S307635. PMID: 33911892; PMCID: PMC8071694.  https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8071694/ (Full text)