Tag: EBV antibody response

Evidence for active Epstein-Barr virus infection in patients with persistent, unexplained illnesses: elevated anti-early antigen antibodies

Abstract:

Forty-four patients, including 26 adults and 18 children under 15 years of age, were referred for evaluation of recurrent or persistent illnesses, with symptoms including pharyngitis, lymphadenopathy, fever, headaches, arthralgia, fatigue, depression, dyslogia, and myalgia. Thirty-nine patients were positive for Epstein-Barr virus antibody with antibody levels compatible with active infection for at least 1 year. Antiviral capsid antigen and anti-early antigen titers of patients were significantly greater (p less than 0.001) than age-group-matched controls. The frequency, number, duration, and patterns of symptoms, as well as patient sex, were compared by age in study patients seropositive and seronegative for Epstein-Barr virus. Illness patterns were not associated with changes in specific antibody titers or clinical findings. Lymphocyte phenotype and function analyses were done in 11 of the 39 patients positive for Epstein-Barr virus antibody; no consistent differences from normal were found. Only 1 of 32 patients had circulating interferon, in contrast to 7 of 7 patients with acute infectious mononucleosis. There were many adverse consequences of the illness. Epstein-Barr virus infection may not be self-limiting, and the virus may be associated with clinically recognizable illness other than infectious mononucleosis in children as well as in adults.

Source:Jones JF, Ray CG, Minnich LL, Hicks MJ, Kibler R, Lucas DO. Evidence for active Epstein-Barr virus infection in patients with persistent, unexplained illnesses: elevated anti-early antigen antibodies. Ann Intern Med. 1985 Jan;102(1):1-7. doi: 10.7326/0003-4819-102-1-. PMID: 2578266. https://pubmed.ncbi.nlm.nih.gov/2578266/

Revisiting IgG antibody reactivity to Epstein-Barr virus in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome and its potential application to disease diagnosis

Abstract:

Infections by the Epstein-Barr virus (EBV) are often at the disease onset of patients suffering from Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS). However, serological analyses of these infections remain inconclusive when comparing patients with healthy controls. In particular, it is unclear if certain EBV-derived antigens eliciting antibody responses have a biomarker potential for disease diagnosis. With this purpose, we re-analysed a previously published microarray data on the IgG antibody responses against 3,054 EBV-related antigens in 92 patients with ME/CFS and 50 HCs.

This re-analysis consisted of constructing different regression models for binary outcomes with the ability to classify patients and HCs. In these models, we tested for a possible interaction of different antibodies with age and gender. When analyzing the whole data set, there were no antibody responses that could be used to distinguish patients from healthy controls. A similar finding was obtained when comparing patients with noninfectious or unknown disease trigger to healthy controls.

However, when data analysis was restricted to the comparison between HCs and patients with a putative infection at disease onset, we could identify stronger antibody responses against two candidate antigens (EBNA4_0529 and EBNA6_0070). Using antibody responses to these two antigens together with age and gender, the final classification model had an estimated sensitivity and specificity of 0.833 and 0.720, respectively.

This reliable case-control discrimination suggested the use of the antibody levels related to these candidate viral epitopes as biomarkers for disease diagnosis in this subgroup of patients. When a bioinformatic analysis was performed on these epitopes, it revealed a potential molecular mimicry with several human proteins. To confirm these promising findings, a follow-up study will be conducted in a separate cohort of patients.

Source: Nuno Sepúlveda, João Malato, Franziska Sotzny, Anna D Grabowska, André Fonseca, Clara Cordeiro, Luís Graça, Przemyslaw Biecek, Uta Behrends, Josef Mautner, Francisco Westermeier, Eliana M Lacerda, Carmen Scheibenbogen. Revisiting IgG antibody reactivity to Epstein-Barr virus in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome and its potential application to disease diagnosis, medRxiv 2022.04.20.22273990; doi: https://doi.org/10.1101/2022.04.20.22273990 https://www.medrxiv.org/content/10.1101/2022.04.20.22273990v1.full-text (Full text)

Long COVID from rheumatology perspective: a simple mimicker or promoter of autoimmunity?

Dear editor,

We have read with great interest the review article by Sapkota et al. which has been recently published in the Clinical Rheumatology journal dealing with long COVID []. In this paper, the authors reported the symptoms and immunological findings of patients who were infected from severe acute respiratory syndrome coronovirus-2 (SARS-CoV-2). These symptoms and laboratory features share similarities with those of patients suffering from autoimmune rheumatic diseases (ARDs). They concluded that long COVID is a mimicker of ARDs and needs to be excluded to ensure a correct diagnosis [].

Recently, we reported a patient who contracted SARS-CoV-2 infection and developed an erosive seronegative arthritis six months after infection []. Musculoskeletal, cutaneous, and other systemic manifestations, along with the presence of autoantibodies, are frequently observed in these patients. On the other hand, SARS-CoV-2 may trigger autoimmune responses and the development of de-novo manifestations of ARDs, as in our patient []. The pathogenesis of these phenomena is not well defined. One hypothesis implies the presence of autoantibodies against interferon (IFN) type-I, or inborn errors in the type-I IFN immunity [, ]. Another hypothesis is that SARS-CoV-2 might trigger autoimmune responses through molecular mimicry []. Several viruses have been implicated as possible etiological factors for the development of ARDs, mostly systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), and others. Between viruses Epstein-Barr virus (EBV) is implicated in the pathogenesis of the above disorders [, ]. Indeed, EBV can trigger immune responses through molecular mimicry and is a polyclonal activator of B-cells and increases the production of rheumatoid factor (RF). Several studies suggested that molecular mimicry is a possible mechanism responsible for the development of ARDs in SARS-CoV-2 infection [, ]. Thus, SARS-CoV-2 may trigger autoimmunity and the possible development of the de novo manifestations of ARDs.

Read the full article HERE.

Source: Drosos AA, Pelechas E, Voulgari PV. Long COVID from rheumatology perspective: a simple mimicker or promoter of autoimmunity? Clin Rheumatol. 2022 Feb 11:1–2. doi: 10.1007/s10067-022-06092-4. Epub ahead of print. PMID: 35147823; PMCID: PMC8831874. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8831874/ (Full text)

Commentary: Antibodies to Human Herpesviruses in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Patients

Introduction: Studies to ascertain a possible relationship between herpesviruses and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) have relied heavily on classical approaches, specifically, serological examination for antibodies against virus proteins, primarily structural, and/or increases in viral load (1–21). These data have been conflicting due in part to several features: the heterogeneity of the disease, high prevalence of the herpesviruses in the population since they can establish lifelong infections, and differences between laboratories. Two additional problems lead to conflicting data in serological studies: which viral antigens are to be used for detection, and what is the possible relationship, if any, of these viral antigens to ME/CFS? These are important questions that must be addressed for any data to provide meaningful insight into the possible contribution of a virus to the pathophysiology of ME/CFS. Although the experimental techniques used in Blomberg’s serological study were appropriate, the selection of specific herpesviruses and viral antigens studied gives a limited view of the humoral response in ME/CFS.

Discussion: Blomberg et al. (22) used a suspension multiplex immunoassay to detect antibodies against various herpesviruses’ antigens, derived from proteins expressed during latency or late lytic replication (Figure 1), with the goal of determining differences in antibody titers against these antigens between ME/CFS patients and controls. However, no rationale was given as to why these particular antigens were chosen and what association, if any, they may have with ME/CFS. This is important because the antigenic properties of the different virus proteins are not the same. As demonstrated in an eloquent study by Vaider-Shalt et al. (23), over the course of their evolution, herpes simplex virus 1 (HSV-1), Epstein-Barr virus (EBV), human herpesvirus 8 (HHV-8), and human cytomegalovirus have decreased the number of epitopes present in virus proteins in order to help them avoid immune detection. Thus, the ability of a virus protein to generate an antibody response is dependent upon the amount of protein present in the host and its antigenicity. It is also not clear why Blomberg et al. (22) included HSV-1/2, human cytomegalovirus, HHV-7, and varicella zoster virus (VZV) in their study since there are no up-to-date literature reports establishing a serological relationship between these viruses and ME/CFS.

Source: Ariza ME. Commentary: Antibodies to Human Herpesviruses in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Patients. Front Immunol. 2020;11:1400. Published 2020 Jul 23. doi:10.3389/fimmu.2020.01400 https://www.frontiersin.org/articles/10.3389/fimmu.2020.01400/full (Full text)

Serological profiling of the EBV immune response in Chronic Fatigue Syndrome using a peptide microarray

Abstract:

BACKGROUND: Epstein-Barr-Virus (EBV) plays an important role as trigger or cofactor for various autoimmune diseases. In a subset of patients with Chronic Fatigue Syndrome (CFS) disease starts with infectious mononucleosis as late primary EBV-infection, whereby altered levels of EBV-specific antibodies can be observed in another subset of patients.

METHODS: We performed a comprehensive mapping of the IgG response against EBV comparing 50 healthy controls with 92 CFS patients using a microarray platform. Patients with multiple sclerosis (MS), systemic lupus erythematosus (SLE) and cancer-related fatigue served as controls. 3054 overlapping peptides were synthesised as 15-mers from 14 different EBV proteins. Array data was validated by ELISA for selected peptides. Prevalence of EBV serotypes was determined by qPCR from throat washing samples.

RESULTS: EBV type 1 infections were found in patients and controls. EBV seroarray profiles between healthy controls and CFS were less divergent than that observed for MS or SLE. We found significantly enhanced IgG responses to several EBNA-6 peptides containing a repeat sequence in CFS patients compared to controls. EBNA-6 peptide IgG responses correlated well with EBNA-6 protein responses. The EBNA-6 repeat region showed sequence homologies to various human proteins.

CONCLUSION: Patients with CFS had a quite similar EBV IgG antibody response pattern as healthy controls. Enhanced IgG reactivity against an EBNA-6 repeat sequence and against EBNA-6 protein is found in CFS patients. Homologous sequences of various human proteins with this EBNA-6 repeat sequence might be potential targets for antigenic mimicry.

Source: Loebel M, Eckey M, Sotzny F, Hahn E, Bauer S, Grabowski P, Zerweck J, Holenya P, Hanitsch LG, Wittke K, Borchmann P, Rüffer JU, Hiepe F, Ruprecht K, Behrends U, Meindl C, Volk HD, Reimer U, Scheibenbogen C. Serological profiling of the EBV immune response in Chronic Fatigue Syndrome using a peptide microarray. PLoS One. 2017 Jun 12;12(6):e0179124. doi: 10.1371/journal.pone.0179124. eCollection 2017. http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0179124 (Full article)