Longitudinal immunomonitoring following Tocilizumab in rheumatoid arthritis

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Response to Treatment and Disease Progression Linked to CD4+ T Cell Surface CC Chemokine Receptor 5 Density in Human Immunodeficiency Virus Type 1 Vertical Infection

The factors governing interindividual variability in disease progression among children vertically infected with human immunodeficiency virus type 1 (HIV-1) remain unclear. Because it has recently been shown in infected adults that the density of CC chemokine receptor 5 (CCR5) molecules at the surface of nonactivated (human leukocyte antigen [HLA]-DR-) CD4+ T cells correlates with disease progression, the same correlation was sought in children. HLA-DR-CD4+ T cell surface CCR5 density was constant over time and correlated with the bioclinical stage and with the CD4 cell slope observed before antiretroviral treatment. In addition, CCR5 density was negatively correlated with the intensity of the decrease in viremia during antiretroviral therapy and was positively correlated with CD4 cell slope since birth. These results are compatible with the hypothesis that CCR5 density is a key factor governing disease progression in pediatric HIV-1 infection and, thereby, an indicator of prognosis. Moreover, they suggest that therapies aimed at reducing CCR5 accessibility should slow down HIV disease evolution in childre

Phenotype Frequencies of Autosomal Minor Histocompatibility Antigens Display Significant Differences among Populations

Minor histocompatibility (H) antigens are allogeneic target molecules having significant roles in alloimmune responses after human leukocyte antigen–matched solid organ and stem cell transplantation (SCT). Minor H antigens are instrumental in the processes of transplant rejection, graft-versus-host disease, and in the curative graft-versus-tumor effect of SCT. The latter characteristic enabled the current application of selected minor H antigens in clinical immunotherapeutic SCT protocols. No information exists on the global phenotypic distribution of the currently identified minor H antigens. Therefore, an estimation of their overall impact in human leukocyte antigen–matched solid organ and SCT in the major ethnic populations is still lacking. For the first time, a worldwide phenotype frequency analysis of ten autosomal minor H antigens was executed by 31 laboratories and comprised 2,685 randomly selected individuals from six major ethnic populations. Significant differences in minor H antigen frequencies were observed between the ethnic populations, some of which appeared to be geographically correlated

5′ and 3′ untranslated regions contribute to the differential expression of specific HLA-A alleles

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Lymphocyte-derived interleukin-17A adds another brick in the wall of inflammation-induced breast carcinogenesis

International audienceWe have previously reported that a subset of breast tumors are infiltrated with IL-17A-producing tumor-associated lymphocytes and that IL-17A cytokine is principally associated with estrogen receptor negative (ER-) and triple negative, basal-like tumors. We established that IL-17A producing lymphocytes induced cancer cell proliferation, chemoresistance, and invasion, indicating that IL-17A is a potential therapeutic target for breast malignancies

CD39: A complementary target to immune checkpoints to counteract tumor-mediated immunosuppression

International audienceWe report that CD39-expressing-melanoma cells inhibited both T-cell proliferation and the generation of cytotoxic effectors in an adenosine-dependent manner, and that treatment with a CD39-blocking antibody alleviated tumor-mediated immunosuppression. Thus, blocking CD39 ectonucleotidase may represent a novel immunotherapeutic strategy to restore antitumor immunity

Emerging clinical phenotypes associated with anti-cytokine autoantibodies

International audienceAnti-cytokine autoantibodies (AAbs) are frequent and involve a very large panel of cytokines both in healthy subjects and in patients with various pathological conditions. In healthy individuals, anti-cytokine AAbs are described as a part of the natural AAb repertoire and are thought to contribute to the fine regulation of cytokine homeostasis. In some patients, neutralizing AAbs targeting cytokines required for the immune protection against specific microbes may induce acquired immunodeficiency leading to very specific infectious phenotypes. For instance, anti-IFNγ AAbs may induce disseminated non-tuberculous mycobacterial infections; anti-IL-17 AAbs are associated with the development of chronic mucosal candidiasis, and anti-IL-6 AAbs with severe staphylococcal or streptococcal infections. In patients with autoimmune diseases, AAbs directed against pathogenic cytokines are able to influence the course of the diseases. In lupus patients, neutralizing anti-IFNα and anti-TNFα AAbs are associated with a decreased bioactivity of the corresponding cytokine and a lower disease severity. Similarly, anti-IL-1α AAbs are associated with nondestructive forms of chronic polyarthritis. More surprisingly, neutralizing anti-BAFF AAbs are observed in the serum of lupus patients with elevated IFNα signature and higher disease activity. In this review, we summarize the current literature describing the different phenotypes and the main mechanisms associated with the occurrence of anti-cytokine AAbs

Une nouvelle génération d’immunothérapies ciblant la voie CD39/CD73/adénosine pour favoriser la réponse immunitaire anti-tumorale

International audienceNo abstract availabl

Specific overexpression of rheumatoid arthritis-associated HLA-DR alleles and presentation of low-affinity peptides.

International audienceObjective To compare levels of HLA–DR expression in rheumatoid arthritis (RA) patients and healthy controls for whom an ordered expression according to the DR alleles is demonstrated and to test the functional consequences of this expression on peptide presentation. Methods Using monoclonal antibodies that recognize different DRB1 alleles, DR molecules were quantitated at the surface of the peripheral blood B cells of 23 RA patients and 17 healthy subjects. The functional consequences of the level of DR surface expression was tested using a universal model of antigen presentation and mutated peptides with variable affinities for the T cell receptor. Results In healthy subjects, surface HLA–DR molecules were expressed at different levels according to allele (DR53, DR4, and DR11 less than DR1 less than DR7 less than DR15). In RA patients, this hierarchy was not conserved and, furthermore, the density of RA‐associated DR4 and DR1 molecules was enhanced in patients compared with the basal density in healthy individuals. We demonstrated that an increased expression of DR molecules at the surface of antigen‐presenting cells allowed a noteworthy presentation of low‐affinity peptides that under normal conditions are not efficient in generating a T cell response at physiologic surface density of the DR molecules. Conclusion Our results suggest that the specific overexpression of RA‐associated HLA molecules could be responsible for the presentation of low‐affinity autopeptides and therefore the activation of peripheral autoreactive T cells

Effects of alcohol withdrawal on monocyte subset defects in chronic alcohol users

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