Tag: IgA

Persistent immune and clotting dysfunction detected in saliva and blood plasma after COVID-19

Abstract:

A growing number of studies indicate that coronavirus disease 2019 (COVID-19) is associated with inflammatory sequelae, but molecular signatures governing the normal versus pathologic convalescence process have not been well-delineated. Here, we characterized global immune and proteome responses in matched plasma and saliva samples obtained from COVID-19 patients collected between 20 and 90 days after initial clinical symptoms resolved.

Convalescent subjects showed robust total IgA and IgG responses and positive antibody correlations in saliva and plasma samples. Shotgun proteomics revealed persistent inflammatory patterns in convalescent samples including dysfunction of salivary innate immune cells, such as neutrophil markers (e.g., myeloperoxidase), and clotting factors in plasma (e.g., fibrinogen), with positive correlations to acute COVID-19 disease severity. Saliva samples were characterized by higher concentrations of IgA, and proteomics showed altered myeloid-derived pathways that correlated positively with SARS-CoV-2 IgA levels.

Beyond plasma, our study positions saliva as a viable fluid to monitor normal and aberrant immune responses including vascular, inflammatory, and coagulation-related sequelae.

Source: Jang H, Choudhury S, Yu Y, Sievers BL, Gelbart T, Singh H, Rawlings SA, Proal A, Tan GS, Qian Y, Smith D, Freire M. Persistent immune and clotting dysfunction detected in saliva and blood plasma after COVID-19. Heliyon. 2023 Jul 4;9(7):e17958. doi: 10.1016/j.heliyon.2023.e17958. PMID: 37483779; PMCID: PMC10362241. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10362241/ (Full text)

Investigating antibody reactivity to the intestinal microbiome in severe myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS)

Abstract:

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a multisystemic disease of unknown aetiology that is characterised by disabling chronic fatigue and involves both the immune and gastrointestinal (GI) systems. Patients display alterations in GI microbiome with a significant proportion experiencing GI discomfort and pain and elevated blood biomarkers for altered intestinal permeability compared with healthy individuals.

To investigate a possible GI origin of ME/CFS we designed a feasibility study to test the hypothesis that ME/CFS pathogenesis is a consequence of increased intestinal permeability that results in microbial translocation and a breakdown in immune tolerance leading to generation of antibodies reactive to indigenous intestinal microbes. Secretory IgA and serum IgG levels and reactivity to intestinal microbes were assessed in five pairs of severe ME/CFS patients and matched same-household healthy controls. For profiling serum IgG we developed IgG-Seq which combines flow-cytometry based bacterial cell sorting and metagenomics to detect mucosal IgG reactivity to the microbiome.

We uncovered evidence for immune dysfunction in severe ME/CFS patients that was characterised by reduced capacity and reactivity of serum IgG to stool microbes, irrespective of their source. This study provides the rationale for additional studies in larger cohorts of ME/CFS patients to further explore immune-microbiome interactions.

Source: Katharine A. Seton, Marianne Defernez, Andrea Telatin, Sumeet K. Tiwari, George M. Savva, Antonietta Hayhoe, Alistair Noble, Ana Carvalho, Steve James, Amolak Bansal, Thomas Wileman, Simon R. Carding. Investigating antibody reactivity to the intestinal microbiome in severe myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). medRxiv 2023.05.21.23290299; doi: https://doi.org/10.1101/2023.05.21.23290299 https://www.medrxiv.org/content/10.1101/2023.05.21.23290299v1.full-text (Full text)

Chronic fatigue syndrome–a controlled cross-sectional study

Abstract:

Twenty-one patients fulfilling the Center for Disease Control criteria for chronic fatigue syndrome (CFS) were examined in a controlled study. Viral antibodies and tests evaluating the immune system were investigated in the patients and in a control group of 21 sex- and age-matched individuals.

Production in vitro of the predominantly T-cell-derived cytokines interleukin-2 and interferon-gamma was significantly higher in patients with CFS compared the control group. Furthermore, the serum concentrations of IgA and IgE were significantly lower in patients with CFS; however, the values were within the normal reference range.

All other variables were similar in the two groups. This study does not suggest a clearly disordered immune system or a chronic viral infection as a major pathogenetic factor in CFS. Longitudinal studies of immunological and virological parameters in CFS are warranted as are studies on patients that are severely handicapped.

Comment in: [Chronic fatigue syndrome and angiotensin-converting enzyme]. [Ugeskr Laeger. 1995]

 

Source: Rasmussen AK, Nielsen H, Andersen V, Barington T, Bendtzen K, Hansen MB, Nielsen L, Pedersen BK, Wiik A. Chronic fatigue syndrome–a controlled cross-sectional study. Ugeskr Laeger. 1994 Nov 14;156(46):6836-40. [Article in Danish] http://www.ncbi.nlm.nih.gov/pubmed/7839498

 

Chronic fatigue syndrome–a controlled cross sectional study

Abstract:

OBJECTIVE: To look for signs of immunodeficiencies and/or longstanding infections underlying chronic fatigue syndrome (CFS).

METHODS: Twenty-one patients fulfilling the Centers for Disease Control criteria for CFS were compared to 21 age and sex matched controls. A number of viral antibodies as well as the following tests evaluating the immune system were studied: autoantibody profile, cell surface markers on isolated blood mononuclear cells, cytokine production, lymphocyte proliferative responses, natural killer cell activity and quantitation of immunoglobulin secreting cells.

RESULTS: Production in vitro of the predominantly T cell derived cytokines interleukin 2 and interferon gamma was significantly higher in patients with CFS compared to the control group. Furthermore, the serum concentrations of IgA and IgE were lower in patients with CFS; however, this difference was caused by a larger number with values of IgA and IgE above the upper limit of the normal range among the controls than among the patients with CFS. All other variables were similar in the 2 groups.

CONCLUSION: A pathogenically significant imbalance of the immune system in patients with CFS cannot be excluded. However, evidence of a causal link between abnormal immunity and CFS was not obtained.

 

Source: Rasmussen AK, Nielsen H, Andersen V, Barington T, Bendtzen K, Hansen MB, Nielsen L, Pedersen BK, Wiik A. J Rheumatol. 1994 Aug;21(8):1527-31. http://www.ncbi.nlm.nih.gov/pubmed/7983659