Excessive neutrophil recruitment promotes typical T-helper 17 responses in Coronavirus disease 2019 patients.

Coronavirus disease 2019 (COVID-19) is caused by a recently identified virus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the disease is a pandemic. Although the hallmarks of severe COVID-19 have been established, the underlying mechanisms that promote severe pathology have not been thoroughly studied. A better understanding of the immune response in severe COVID-19 patients may help guide the development of therapeutic strategies and predict immuno-pathogenicity. This study was set to determine the lymphocyte and cytokine profiles associated with COVID-19 severity. A total of 43 hospitalised COVID-19 patients were recruited for the study and whole blood samples were drawn from each patient. Complete blood counts, lymphocyte subset profiles and C-reactive protein statuses of patients were determined. Cytometric bead array was performed to analyse the cytokine profiles of each patient. The demographic characteristics showed that the median age of the patients was 48.72 years, with an interquartile range from 40 to 60 years, and 69.77% of the patients were male. COVID-19 patients exhibited significantly low CD4+ lymphocyte expansion and leucocytosis augmented by elevated neutrophil and immature granulocytes. Stratification analysis revealed that reduced monocytes and elevated basophils and immature granulocytes are implicated in severe pathology. Additionally, cytokine results were noted to have significant incidences of interleukin 17A (IL-17A) expression associated with severe disease. Results from this study suggest that a systemic neutrophilic environment may preferentially skew CD4+ lymphocytes towards T-helper 17 and IL-17A promotion, thus, aggravating inflammation. Consequently, results from this study suggest broad activity immunomodulation and targeting neutrophils and blocking IL-17 production as therapeutic strategies against severe COVID-19.

Comparison of the specificities of IgG, IgG-subclass, IgA and IgM reactivities in African and European HIV-infected individuals with an HIV-1 clade C proteome-based array.

A comprehensive set of recombinant proteins and peptides of the proteome of HIV-1 clade C was prepared and purified and used to measure IgG, IgG-subclass, IgA and IgM responses in HIV-infected patients from Sub-Saharan Africa, where clade C is predominant. As a comparison group, HIV-infected patients from Europe were tested. African and European patients showed an almost identical antibody reactivity profile in terms of epitope specificity and involvement of IgG, IgG subclass, IgA and IgM responses. A V3-peptide of gp120 was identified as major epitope recognized by IgG1>IgG2 = IgG4>IgG3, IgA>IgM antibodies and a C-terminal peptide represented another major peptide epitope for the four IgG subclasses. By contrast, gp41-derived-peptides were mainly recognized by IgG1 but not by the other IgG subclasses, IgA or IgM. Among the non-surface proteins, protease, reverse transcriptase+RNAseH, integrase, as well as the capsid and matrix proteins were the most frequently and strongly recognized antigens which showed broad IgG subclass and IgA reactivity. Specificities and magnitudes of antibody responses in African patients were stable during disease and antiretroviral treatment, and persisted despite severe T cell loss. Using a comprehensive panel of gp120, gp41 peptides and recombinant non-surface proteins of HIV-1 clade C we found an almost identical antibody recognition profile in African and European patients regarding epitopes and involved IgG-sublass, IgA- and IgM-responses. Immune recognition of gp120 peptides and non-surface proteins involved all four IgG subclasses and was indicative of a mixed Th1/Th2 immune response. The HIV-1 clade C proteome-based test allowed diagnosis and monitoring of antibody responses in the course of HIV-infections and assessment of isotype and subclass responses.

Persistence of IgE-associated allergy and allergen-specific IgE despite CD4+ T cell loss in AIDS.

The infection of CD4+ cells by HIV leads to the progressive destruction of CD4+ T lymphocytes and, after a severe reduction of CD4+ cells, to AIDS. The aim of the study was to investigate whether HIV-infected patients with CD4 cell counts <200 cells/µl can suffer from symptoms of IgE-mediated allergy, produce allergen-specific IgE antibody responses and show boosts of allergen-specific IgE production. HIV-infected patients with CD4 counts ≤ 200 cells/µl suffering from AIDS and from IgE-mediated allergy were studied. Allergy was diagnosed according to case history, physical examination, skin prick testing (SPT), and serological analyses including allergen microarrays. HIV infection was confirmed serologically and the disease was staged clinically. The predominant allergic symptoms in the studied patients were acute allergic rhinitis (73%) followed by asthma (27%) due to IgE-mediated mast cell activation whereas no late phase allergic symptoms such as atopic dermatitis, a mainly T cell-mediated skin manifestation, were found in patients suffering from AIDS. According to IgE serology allergies to house dust mites and grass pollen were most common besides IgE sensitizations to various food allergens. Interestingly, pollen allergen-specific IgE antibody levels in the patients with AIDS and in additional ten IgE-sensitized patients with HIV infections and low CD4 counts appeared to be boosted by seasonal allergen exposure and were not associated with CD4 counts. Our results indicate that secondary allergen-specific IgE production and IgE-mediated allergic inflammation do not require a fully functional CD4+ T lymphocyte repertoire.