2021 – Page 11 – American ME and CFS Society

Associations Between Psychological and Immunological Variables in Chronic Fatigue Syndrome/Myalgic Encephalomyelitis: A Systematic Review

Abstract:

Background: Little emphasis has been given to the fact that various psychological processes and behaviors in chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) have neural correlates that affect-and are affected by-the immune system. The aim of this paper is to provide a systematic review of the literature on cross-sectional and longitudinal associations between psychological and immunological variables/changes in CFS/ME.

Methods: The systematic literature search was conducted on Dec 10, 2020 using PubMed. Original research studies investigating associations between a predefined set of psychological and immunological variables in CFS/ME were included. Specifically, the review was focused on studies examining the following psychological variables: executive function, emotion regulation, interpersonal function, sleep, mental health, anxiety, depression, and/or other psychiatric symptoms. In terms of immunological variables, studies investigating interleukin (IL)-1, IL-2, IL-4, IL-6, tumor necrosis factor (TNF), CD4⁺, and/or CD8⁺ were included. Besides original research papers, other potentially relevant papers (e.g., literature reviews) were carefully read and reference lists were checked in order to identify any additional relevant studies. Available data was summarized in text and tables.

Results: The literature search identified 897 potentially relevant papers. Ultimately, 14 studies (807 participants in total) were included in the review of which only two were longitudinal in nature. The review indicated that executive function is associated with IL-1 and IL-6, and interpersonal function is associated with IL-6 and TNF-α. Further, the available data suggested that emotion regulation is associated with IL-2 and sleep is associated with IL-1, IL-6, TNF-α, and IL-2. Interestingly, poorer emotion regulation, interpersonal function, and sleep have all been found to be associated with higher cytokine levels. Executive function has shown both positive and negative relationships with cytokines and among these psychological constructs, it is also the only one that has been found to be associated with CD4⁺ and CD8⁺ counts/percentages.

Conclusions: Correlations exist between psychological and immunological variables in CFS/ME. However, there are few consistent findings and there is almost a complete lack of longitudinal studies. This review points to a gap in existing CFS/ME research and hopefully, it will inspire to the generation of innovative, psychoneuroimmunological hypotheses within the CFS/ME research field.

Source: Raanes EFW, Stiles TC. Associations Between Psychological and Immunological Variables in Chronic Fatigue Syndrome/Myalgic Encephalomyelitis: A Systematic Review. Front Psychiatry. 2021 Nov 23;12:716320. doi: 10.3389/fpsyt.2021.716320. PMID: 34887782; PMCID: PMC8650213. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8650213/ (Full text)

Breast implant illness: scientific evidence of its existence

Abstract:

Introduction: More than one million breast augmentation procedures using silicone breast implants (SBI) have been performed worldwide. Adverse events of SBI include local complications such as pain, swelling, redness, infections, capsular contracture, implant rupture and gel-bleed. Furthermore, patients experience systemic symptoms such as chronic fatigue, arthralgias, myalgias, pyrexia, sicca, and cognitive dysfunction. These symptoms received different names such as autoimmune/inflammatory syndrome induced by adjuvants (ASIA) due to silicone incompatibility syndrome and breast implant illness (BII). Because of chronic immune activation, BII/ASIA, allergies, autoimmune diseases, immune deficiencies and finally lymphomas may develop in SBI patients.

Areas covered: Causality for SBI-related BII/ASIA is reviewed. To address the role of silicone implants in promoting causality, we utilized the Bradford-Hill criteria, with results highlighted in this article.

Expert opinion: We conclude that there is a causal association between SBIs and BII/ASIA. Using data derived from patients with BII/ASIA and from other medically implanted devices, there appears to be clear pathogenic relationship between SBI and BII/ASIA. Breast implants cause characteristic systemic reactions in certain women, leading to symptoms of sufficient severity to warrant device removal. The morbidity suffered is variable. SBI removal resolves the symptoms in most women and removal is the most effective treatment.

Source: Cohen Tervaert JW, Mohazab N, Redmond D, van Eeden C, Osman M. Breast implant illness: scientific evidence of its existence. Expert Rev Clin Immunol. 2021 Dec 9. doi: 10.1080/1744666X.2022.2010546. Epub ahead of print. PMID: 34882509. https://pubmed.ncbi.nlm.nih.gov/34882509/

TLR Antagonism by Sparstolonin B Alters Microbial Signature and Modulates Gastrointestinal and Neuronal Inflammation in Gulf War Illness Preclinical Model

Abstract:

The 1991 Persian Gulf War veterans presented a myriad of symptoms that ranged from chronic pain, fatigue, gastrointestinal disturbances, and cognitive deficits. Currently, no therapeutic regimen exists to treat the plethora of chronic symptoms though newer pharmacological targets such as microbiome have been identified recently. Toll-like receptor 4 (TLR4) antagonism in systemic inflammatory diseases have been tried before with limited success, but strategies with broad-spectrum TLR4 antagonists and their ability to modulate the host-microbiome have been elusive.

Using a mouse model of Gulf War Illness, we show that a nutraceutical, derived from a Chinese herb Sparstolonin B (SsnB) presented a unique microbiome signature with an increased abundance of butyrogenic bacteria. SsnB administration restored a normal tight junction protein profile with an increase in Occludin and a parallel decrease in Claudin 2 and inflammatory mediators high mobility group box 1 (HMGB1), interleukin-1β (IL-1β), and interleukin-6 (IL-6) in the distal intestine. SsnB also decreased neuronal inflammation by decreasing IL-1β and HMGB1, while increasing brain-derived neurotrophic factor (BDNF), with a parallel decrease in astrocyte activation in vitro.

Mechanistically, SsnB inhibited the binding of HMGB1 and myeloid differentiation primary response protein (MyD88) to TLR4 in the intestine, thus attenuating TLR4 downstream signaling. Studies also showed that SsnB was effective in suppressing TLR4-induced nod-like receptor protein 3 (NLRP3) inflammasome activation, a prominent inflammatory disease pathway. SsnB significantly decreased astrocyte activation by decreasing colocalization of glial fibrillary acid protein (GFAP) and S100 calcium-binding protein B (S100B), a crucial event in neuronal inflammation. Inactivation of SsnB by treating the parent molecule by acetate reversed the deactivation of NLRP3 inflammasome and astrocytes in vitro, suggesting that SsnB molecular motifs may be responsible for its anti-inflammatory activity.

Source: Bose D, Mondal A, Saha P, Kimono D, Sarkar S, Seth RK, Janulewicz P, Sullivan K, Horner R, Klimas N, Nagarkatti M, Nagarkatti P, Chatterjee S. TLR Antagonism by Sparstolonin B Alters Microbial Signature and Modulates Gastrointestinal and Neuronal Inflammation in Gulf War Illness Preclinical Model. Brain Sci. 2020 Aug 8;10(8):532. doi: 10.3390/brainsci10080532. PMID: 32784362; PMCID: PMC7463890. https://www.mdpi.com/2076-3425/10/8/532 (Full text)

COVID-19 and Chronic Fatigue Syndrome: An Endocrine Perspective

Abstract:

Patients recovering from COVID-19 may have persistent debilitating symptoms requiring long term support through individually tailored cardiopulmonary and psychological rehabilitation programs. Clinicians need to be aware about the likely long-term complications and their diagnostic assessments to help identify any occult problems requiring additional help. Endocrinological evaluations should be considered as part of the armamentarium in the management of such individuals with diligent cognizance about the involvement of the hypothalamo-pituitary-adrenal (HPA) axis, adrenals, and thyroid.

Source: Bansal R, Gubbi S, Koch CA. COVID-19 and Chronic Fatigue Syndrome: An Endocrine Perspective. J Clin Transl Endocrinol. 2021 Dec 3:100284. doi: 10.1016/j.jcte.2021.100284. Epub ahead of print. PMID: 34877261; PMCID: PMC8641402. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8641402/ (Full text)

Nationwide epidemiological characteristics of chronic fatigue syndrome in South Korea

Abstract:

Background: Chronic fatigue syndrome (CFS) is a long-term disabling illness accompanied by medically unexplained fatigue. This study aimed to explore the epidemiological characteristics of CFS in South Korea.

Methods: Using the nationwide medical records provided by the Korean Health Insurance Review & Assessment Service (HIRA), we analyzed the entire dataset for CFS patients diagnosed by physicians in South Korea from January 2010 to December 2020.

Results: The annual mean incidence of CFS was estimated to be 44.71 ± 6.10 cases per 100,000 individuals [95% CI: 40.57, 48.76], and the prevalence rate was 57.70 ± 12.20 cases per 100,000 individuals [95% CI: 49.40, 65.79]. These two rates increased by 1.53- and 1.94-fold from 2010 to 2020, respectively, and showed an increasing trend with aging and an approximately 1.5-fold female predominance.

Conclusions: This study is the first to report the nationwide epidemiological features of CFS, which reflects the clinical reality of CFS diagnosis and care in South Korea. This study will be a valuable reference for studies of CFS in the future.

Source: Lim EJ, Lee JS, Lee EJ, Jeong SJ, Park HY, Ahn YC, Son CG. Nationwide epidemiological characteristics of chronic fatigue syndrome in South Korea. J Transl Med. 2021 Dec 7;19(1):502. doi: 10.1186/s12967-021-03170-0. PMID: 34876158. https://pubmed.ncbi.nlm.nih.gov/34876158/

The effects of traditional Chinese manual therapy (Tuina) for chronic fatigue syndrome: A protocol for systematic review and meta-analysis

Abstract:

Background: Chronic fatigue syndrome (CFS) is a common disease and characterized by fatigue, exhaustion, heavy limbs, and dizziness. Tuina, as a traditional Chinese manual therapy, is usually used for CFS in China. Several studies have reported that Tuina can improve fatigue exhaustion, and dizziness of patients with CFS. However, the effects of Tuina for CFS still remain controversial. Therefore, the current systematic review and meta-analysis will be conducted to investigate the effects of Tuina in the management of CFS.

Methods: The comprehensive electronic search of PubMed, Web of Science, Chinese National Knowledge Infrastructure, Wanfang Database, Embase, Cochrane Library, Chinese Science Citation Database, Technology Periodical Database from their inception to October 2021 will be conducted. Randomized controlled trials of Tuina for CFS will be included in the review. Two independent reviewers will complete the study selection, data extraction, and the risk of bias. The meta-analysis will be conducted using the Review Manager Version 5.3 software. The heterogeneity will be assessed using the I2 statistic and Q statistic. The standardized mean difference and 95% confidence intervals will be calculated based on different heterogeneity. The subgroup analysis will be conducted based on the duration of treatment, age, gender, duration of CFS. Quality of evidence will be assessed using the Grades of Recommendation, Assessment, Development and Evaluation.

Results: The current systematic review and meta-analysis will be to investigate the effects of Tuina in the management of CFS.

Conclusion: The conclusion of this study will provide the evidence for the treatment of CFS in the future. It is expected that the conclusions drawn from this review will benefit patients, clinical practitioners and policy makers.

Source: Ren J, He T, Zhou X, Wu Z, Kong L. The effects of traditional Chinese manual therapy (Tuina) for chronic fatigue syndrome: A protocol for systematic review and meta-analysis. Medicine (Baltimore). 2021 Nov 5;100(44):e27700. doi: 10.1097/MD.0000000000027700. PMID: 34871257. https://pubmed.ncbi.nlm.nih.gov/34871257/

Chronic fatigue syndrome against the background of the COVID-19 pandemic

Abstract:

The more we learn about the new coronavirus infection, the more we understand that we will feel the echoes of the pandemic for many years, and those who have successfully endured the acute phase of COVID-19 may face the consequences of the infection. One of the most frequent manifestations will be the development of chronic fatigue syndrome (CFS) after COVID-19. This article discusses the possible causes of the development of CFS, as well as possible ways of its treatment and prevention.

Source: Nikitina AJ, Levin OS. Sindrom khronicheskoi ustalosti na fone pandemii COVID-19 [Chronic fatigue syndrome against the background of the COVID-19 pandemic]. Zh Nevrol Psikhiatr Im S S Korsakova. 2021;121(10. Vyp. 2):92-98. Russian. doi: 10.17116/jnevro202112110292. PMID: 34870921. https://pubmed.ncbi.nlm.nih.gov/34870921/ [in English, Russian]

Case Report: Neutralization of Autoantibodies Targeting G-Protein-Coupled Receptors Improves Capillary Impairment and Fatigue Symptoms After COVID-19 Infection

Abstract:

Clinical features of Coronavirus disease 2019 (COVID-19) are caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Acute infection management is a substantial healthcare issue, and the development of long-Covid syndrome (LCS) is extremely challenging for patients and physicians. It is associated with a variety of characteristics as impaired capillary microcirculation, chronic fatigue syndrome (CFS), proinflammatory cytokines, and functional autoantibodies targeting G-protein-coupled receptors (GPCR-AAbs). Here, we present a case report of successful healing of LCS with BC 007 (Berlin Cures, Berlin, Germany), a DNA aptamer drug with a high affinity to GPCR-AAbs that neutralizes these AAbs.

A patient with a documented history of glaucoma, recovered from mild COVID-19, but still suffered from CFS, loss of taste, and impaired capillary microcirculation in the macula and peripapillary region. He was positively tested for various targeting GPCR-AAbs. Within 48 h after a single BC 007 treatment, GPCR-AAbs were functionally inactivated and remained inactive during the observation period of 4 weeks. This observation was accompanied by constant improvement of the fatigue symptoms of the patient, taste, and retinal capillary microcirculation. Therefore, the removal of GPCR-AAb might ameliorate the characteristics of the LCD, such as capillary impairment, loss of taste, and CFS.

Source: Hohberger B, Harrer T, Mardin C, Kruse F, Hoffmanns J, Rogge L, Heltmann F, Moritz M, Szewczykowski C, Schottenhamml J, Kräter M, Bergua A, Zenkel M, Gießl A, Schlötzer-Schrehardt U, Lämmer R, Herrmann M, Haberland A, Göttel P, Müller J, Wallukat G. Case Report: Neutralization of Autoantibodies Targeting G-Protein-Coupled Receptors Improves Capillary Impairment and Fatigue Symptoms After COVID-19 Infection. Front Med (Lausanne). 2021 Nov 18;8:754667. doi: 10.3389/fmed.2021.754667. PMID: 34869451; PMCID: PMC8637609. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8637609/ (Full text)

Epstein-Barr Virus and the Origin of Myalgic Encephalomyelitis or Chronic Fatigue Syndrome

Abstract:

Myalgic encephalomyelitis or chronic fatigue syndrome (ME/CFS) affects approximately 1% of the general population. It is a chronic, disabling, multi-system disease for which there is no effective treatment. This is probably related to the limited knowledge about its origin. Here, we summarized the current knowledge about the pathogenesis of ME/CFS and revisit the immunopathobiology of Epstein-Barr virus (EBV) infection. Given the similarities between EBV-associated autoimmune diseases and cancer in terms of poor T cell surveillance of cells with EBV latency, expanded EBV-infected cells in peripheral blood and increased antibodies against EBV, we hypothesize that there could be a common etiology generated by cells with EBV latency that escape immune surveillance.

Albeit inconclusive, multiple studies in patients with ME/CFS have suggested an altered cellular immunity and augmented Th2 response that could result from mechanisms of evasion to some pathogens such as EBV, which has been identified as a risk factor in a subset of ME/CFS patients. Namely, cells with latency may evade the immune system in individuals with genetic predisposition to develop ME/CFS and in consequence, there could be poor CD4 T cell immunity to mitogens and other specific antigens, as it has been described in some individuals.

Ultimately, we hypothesize that within ME/CFS there is a subgroup of patients with DRB1 and DQB1 alleles that could confer greater susceptibility to EBV, where immune evasion mechanisms generated by cells with latency induce immunodeficiency. Accordingly, we propose new endeavors to investigate if anti-EBV therapies could be effective in selected ME/CFS patients.

Source: Ruiz-Pablos M, Paiva B, Montero-Mateo R, Garcia N, Zabaleta A. Epstein-Barr Virus and the Origin of Myalgic Encephalomyelitis or Chronic Fatigue Syndrome. Front Immunol. 2021 Nov 15;12:656797. doi: 10.3389/fimmu.2021.656797. PMID: 34867935; PMCID: PMC8634673. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8634673/ (Full text)