The development of vaccines and effective diagnostic methods for bovine tuberculosis requires an understanding of the immune response against its causative agent, Mycobacterium bovis. Although this disease is primarily investigated and diagnosed through the assessment of cell-mediated immunity, the role of B cells and antibodies in bovine tuberculosis has been relatively undervalued and understudied. Current evidence indicates that circulating M. bovis-specific antibodies are not effective in controlling the disease. However, local humoral immune responses may contribute to either defence or pathology. Recent studies in animal models and cattle vaccine trials suggest a potential beneficial role of B cells in tuberculosis control. This review discusses the role of B cells and antibodies in bovine tuberculosis and explores antibody-based diagnostics for the disease, including traditional techniques, such as different ELISA, new platforms based on multiple antigens and point-of-care technologies. The high specificity and sensitivity values achieved by numerous antibody-based tests support their use as complementary tests for the diagnosis of bovine tuberculosis, especially for identifying infected animals that may be missed by the official tests.

Chronic infections induce CD4+ T-cells with cytotoxic functions (CD4 CTLs); at present, it is still unknown whether latent tuberculosis (LTB) and active tuberculosis (ATB) induce CD4 CTLs. Plasma and cells from four patient groups-uninfected contact (UC), LTB, and ATB (divided as sensitive [DS-TB]- or resistant [DR-TB]-drug)-were evaluated by flow cytometry, q-PCR, and proteomics. The data showed that ATB patients had an increased frequency of CD4+ T-cells and a decreased frequency of CD8+ T-cells. The latter displays an exhausted-like profile characterized by CD39, CD279, and TIM-3 expression. ATB had a high frequency of CD4 + perforin+ cells, suggesting a CD4 CTL profile. The expression (at the transcriptional level) of granzyme A, granzyme B, granulysin, and perforin, as well as the genes T-bet (Tbx21) and NKG2D (Klrk1), in enriched CD4+ T-cells, confirmed the cytotoxic signature of CD4+ T-cells during ATB (which was stronger in DS-TB than in DR-TB). Moreover, proteomic analysis revealed the presence of HSP70 (in DS-TB) and annexin A5 (in DR-TB), which are molecules that have been associated with favoring the CD4 CTL profile. Finally, we found that lipids from Mycobacterium tuberculosis increased the presence of CD4 CTLs in DR-TB patients. Our data suggest that ATB is characterized by exhausted-like CD8+ T-cells, which, together with a specific microenvironment, favor the presence of CD4 CTLs.

Previously, an increase in clinical effectiveness of the antituberculosis treatment (ATT) and antiretroviral therapy (ART) in case of additional immunoglobulin G (IgG) administration in patients with multidrug-resistant tuberculosis (MDR-TB)/HIV coinfection was reported. The aim of this study was to investigate the impact of IgG administration in addition to the standard second-line ATT and ART on the humoral immunity status in patients with MDR-TB/HIV coinfection immune deficiency. The study involved 52 patients living with HIV with MDR-TB coinfection and CD4+ lymphocyte cell count below 50 cells/μCL. Patients in the control group and intervention group received the second-line ATT and ART; in addition, patients in the intervention group received IgG intravenously. The humoral immunity status was evaluated by measurement of IgA, IgE, IgG, and IgM in plasma. The standard ATT and ART resulted in a two-step change in humoral immunity: IgM, IgG, IgA, and IgE levels gradually increased to a maximal level at the 5-month mark and started to gradually decrease after the 8-month mark. Addition of IgG to the standard therapy resulted in a steeper decrease in the immunoglobulin level in serum, especially IgG, compared with standard therapy alone, allowing for an earlier initiation of ART in patients in the intervention group.

Aplastic anemia (AA) and hypoplastic myelodysplastic syndrome are paradigms of autoimmune hematopoietic failure (AHF). Myelodysplastic syndrome and acute myeloid leukemia are unequivocal myeloid neoplasms (MNs). Currently, AA is also known to be a clonal hematological disease. Genetic aberrations typically observed in MNs are detected in approximately one-third of AA patients. In AA patients harboring MN-related genetic aberrations, a poor response to immunosuppressive therapy (IST) and an increased risk of transformation to MNs occurring either naturally or after IST are predicted. Approximately 10%-15% of patients with severe AA transform the disease phenotype to MNs following IST, and in some patients, leukemic transformation emerges during or shortly after IST. Phenotypic transformations between AHF and MNs can occur reciprocally. A fraction of advanced MN patients experience an aplastic crisis during which leukemic blasts are repressed. The switch that shapes the disease phenotype is a change in the strength of extramedullary inflammation. Both AHF and MNs have an immune-active bone marrow (BM) environment (BME). In AHF patients, an inflamed BME can be evoked by infiltrated immune cells targeting neoplastic molecules, which contributes to the BM-specific autoimmune impairment. Autoimmune responses in AHF may represent an antileukemic mechanism, and inflammatory stressors strengthen antileukemic immunity, at least in a significant proportion of patients who have MN-related genetic aberrations. During active inflammatory episodes, normal and leukemic hematopoieses are suppressed, which leads to the occurrence of aplastic cytopenia and leukemic cell regression. The successful treatment of underlying infections mitigates inflammatory stress-related antileukemic activities and promotes the penetration of leukemic hematopoiesis. The effect of IST is similar to that of treating underlying infections. Investigating inflammatory stress-powered antileukemic immunity is highly important in theoretical studies and clinical practice, especially given the wide application of immune-activating agents and immune checkpoint inhibitors in the treatment of hematological neoplasms.

Tuberculosis (TB) is a bacterial infection caused by Mycobacterium tuberculosis (M.tb). B cells are the central mediator of the humoral response; they are responsible for producing antibodies in addition to mediating other functions. The role of the cellular response during the TB spectrum by B cells is still controversial.

In this study, we evaluated the distribution of the circulating B cell subsets in patients with active and latent TB (ATB and LTB, respectively) and how they respond to stimuli of protein or lipid from M.tb.

Here, we show that ATB patients show an immune fingerprinting. However, patients with drug-sensitive- (DS-TB) or drug-resistant- (DR-TB) TB have altered frequencies of circulating B cells. DS-TB and DR-TB display a unique profile characterized by high systemic levels of IFN-γ, IL-10, IgG, IgG/IgM ratio, and total B cells. Moreover, B cells from DR-TB are less efficient in producing IL-10, and both DS-TB and DR-TB produce less IFN-γ in response to M.tb antigens.

These results provide new insights into the population dynamics of the cellular immune response by B cells against M.tb and suggest a fingerprinting to characterize the B-cell response on DR-TB.

Accumulating evidence demonstrates that autoimmune hematopoietic failure and myeloid neoplasms have an intrinsic relationship with regard to clonal hematopoiesis and disease evolution. In approximately 10%-15% of patients with severe aplastic anemia (SAA), the disease phenotype is transformed into myeloid neoplasms following antithymocyte globulin plus cyclosporine-based immunosuppressive therapy. In some of these patients, myeloid neoplasms appear during or shortly after immunosuppressive therapy. Leukemic transformation in SAA patients during anti-tuberculosis treatment has not been reported.

A middle-aged Chinese female had a 6-year history of non-SAA and a 2-year history of paroxysmal nocturnal hemoglobinuria (PNH). With aggravation of systemic inflammatory symptoms, severe pancytopenia developed, and her hemoglobinuria disappeared. Laboratory findings in cytological, immunological and cytogenetic analyses of bone marrow samples met the diagnostic criteria for "SAA." Definitive diagnosis of disseminated tuberculosis was made in the search for infectious niches. Remarkable improvement in hematological parameters was achieved within 1 mo of anti-tuberculosis treatment, and complete hematological remission was achieved within 4 mo of treatment. Frustratingly, the hematological response lasted for only 3 mo, and pancytopenia reemerged. At this time, cytological findings (increased bone marrow cellularity and an increased percentage of myeloblasts that accounted for 16.0% of all nucleated hematopoietic cells), immunological findings (increased percentage of cluster of differentiation 34+ cells that accounted for 12.28% of all nucleated hematopoietic cells) and molecular biological findings (identification of somatic mutations in nucleophosmin-1 and casitas B-lineage lymphoma genes) revealed that "SAA" had transformed into acute myeloid leukemia with mutated nucleophosmin-1. The transformation process suggested that the leukemic clones were preexistent but were suppressed in the PNH and SAA stages, as development of symptomatic myeloid neoplasm through acquisition and accumulation of novel oncogenic mutations is unlikely in an interval of only 7 mo. Aggravation of inflammatory stressors due to disseminated tuberculosis likely contributed to the repression of normal and leukemic hematopoiesis, and the relief of inflammatory stressors due to anti-tuberculosis treatment contributed to penetration of neoplastic hematopoiesis. The concealed leukemic clones in the SAA and PNH stages raise the possibility of an inflammatory stress-fueled antileukemic mechanism.

Aggravated inflammatory stressors can repress normal and leukemic hematopoiesis, and relieved inflammatory stressors can facilitate penetration of neoplastic hematopoiesis.