Follicular T cells are clonally and transcriptionally distinct in B cell-driven mouse autoimmune disease

Pathogenic autoantibodies contribute to tissue damage and clinical decline in autoimmune disease. Follicular T cells are central regulators of germinal centers, although their contribution to autoantibody-mediated disease remains unclear. Here we perform single cell RNA and T cell receptor (TCR) sequencing of follicular T cells in a mouse model of autoantibody-mediated disease, allowing for analyses of paired transcriptomes and unbiased TCRαβ repertoires at single cell resolution. A minority of clonotypes are preferentially shared amongst autoimmune follicular T cells and clonotypic expansion is associated with differential gene signatures in autoimmune disease. Antigen prediction using algorithmic and machine learning approaches indicates convergence towards shared specificities between non-autoimmune and autoimmune follicular T cells. However, differential autoimmune transcriptional signatures are preserved even amongst follicular T cells with shared predicted specificities. These results demonstrate that follicular T cells are phenotypically distinct in B cell-driven autoimmune disease, providing potential therapeutic targets to modulate autoantibody development.

Advancement of antigen-specific immunotherapy: knowledge transfer between allergy and autoimmunity

Targeted restoration of immunological tolerance to self-antigens or innocuous environmental allergens represents the ultimate aim of treatment options in autoimmune and allergic disease. Antigen-specific immunotherapy (ASI) is the only intervention that has proven disease-modifying efficacy as evidenced by induction of long-term remission in a number of allergic conditions. Mounting evidence is now indicating that specific targeting of pathogenic T cells in autoinflammatory and autoimmune settings enables effective restoration of immune homeostasis between effector and regulatory cells and alters the immunological course of disease.Here we discuss the key lessons learned during the development of antigen-specific immunotherapies and how these can be applied to inform future interventions. Armed with this knowledge and current high-throughput technology to track immune cell phenotype and function, it may no longer be a matter of ‘if’ but ‘when’ this ultimate aim of targeted tolerance restoration is realised.

The Multifaceted Nature of Streptococcal Antigen I/II Proteins in Colonization and Disease Pathogenesis

Streptococci are Gram-positive bacteria that belong to the natural microbiota of humans and animals. Certain streptococcal species are known as opportunistic pathogens with the potential to cause severe invasive disease. Antigen I/II (AgI/II) family proteins are sortase anchored cell surface adhesins that are nearly ubiquitous across streptococci and contribute to many streptococcal diseases, including dental caries, respiratory tract infections, and meningitis. They appear to be multifunctional adhesins with affinities to various host substrata, acting to mediate attachment to host surfaces and stimulate immune responses from the colonized host. Here we will review the literature including recent work that has demonstrated the multifaceted nature of AgI/II family proteins, focusing on their overlapping and distinct functions and their important contribution to streptococcal colonization and disease.

SD DENGUE DUO® (NS1, IgG, IgM) RAPID TEST DALAM MENUNJANG DIAGNOSIS INFEKSI VIRUS DENGUE

Dengue virus infection can cause dengue hemorrhagic fever (DHF) which is still a major health problem in Indonesia. Thediagnosis of DHF is established based on WHO criteria and IgM/IgG antidengue serologic markers. A rapid method is needed for thedetecting or screening the disease. Antigen detection (NS1) can be performed by immunochromatography (rapid test) or enzyme -linkedimmunosorbent assay (ELISA). Recently, a rapid test to detect NS1 as an antigen and IgM/IgG antidengue to differentiate primary andsecondary dengue virus infection is available in one cassette. This study evaluated the new commercial dengue rapid test, SD DengueDuo for the detection of both antigen and antibodies to dengue virus. Serum samples used in this study were collected from 33 denguevirus infection patients according to WHO criteria and admitted in the Tropical Ward, Dr. Soetomo Hospital. Samples were taken twice,during acute and convalescent phase. SD Dengue Duo (NS1, IgG, IgM) rapid test was used and confirmed by ELISA as the gold standard.To determine the diagnostic specificity 20 samples of non dengue virus infection (typhoid fever and malaria) confirmed by laboratorytests were used. In the acute phase, SD Dengue Duo (NS1, IgG, IgM) rapid test showed IgG sensitivity 94.7% (18/19), specificity 92.9%(13/14), IgM sensitivity 85% (17/20), specificity 100% (13/13), NS1 sensitivity 50% (10/20), specificity 100% (13/13). In theconvalescent phase, SD Dengue Duo (NS1, IgG, IgM) rapid test showed antidengue IgG sensitivity 96.3% (26/27), specificity 66.7%(4/6), IgM sensitivity 95% (22/23), specificity 80% (8/10), NS1 sensitivity 42.9% (3/7), specificity 100% (26/26). To establish thediagnosis of dengue virus infection, not only NS1, but also antidengue IgM/IgG is needed. SD Dengue Duo containing dengue NS1 antigencombined with IgG/IgM test in one cassette is a rapid, practical and has a high validity diagnostic result.

The immunogenicity of Echinococcus granulosus antigen 5 is determined by its post-translational modifications

Since its early introduction as a marker for the immunodiagnosis of hydatid disease, antigen 5 (Ag5) has been regarded as one of the more relevant antigens of Echinococcus granulosus, and it is still widely used in different confirmation techniques. In this work we prepared 2 recombinant forms of the antigen, namely, rAg5 (corresponding to the unprocessed polypeptide chain of the antigen) and rAg5-38s (corresponding to its 38 kDa subunit). Their antigenicities were compared to that of the native antigen using a human serum collection. There was a major drop in the reactivity of the sera, particularly against rAg5-38s, which was confirmed by analysis of the cross-reactivity of 2 panels of monoclonal antibodies specific for rAg5-38s and the native antigen. Using the chemically deglycosylated native antigen, we demonstrated that the reduced antigenicity of the recombinants is due to the loss of the sugar determinants, and not to their misfolding. Inhibition experiments using phosphorylcholine confirmed that this moiety also contributes to the reactivity of the antigen, but to a much lesser extent. The presence of immunodominant highly cross-reactive glycan moieties in the Ag5 molecule may involve a parasite evasion mechanism.