HLA-C*12:02:62 differs from HLA-C*12:02:02:01 by a single nucleotide change (C > T) at codon 16 in exon-2.

HLA-C*12:449 differs from HLA-C*12:02:02:01 by a single non-synonymous change in exon 7.

The novel HLA-C*04:562 allele differs from HLA-C*04:03:01 by a single non-synonymous change in Exon 4.

The novel HLA-B*40:160:01:02 allele differs from HLA-B*40:160:01:01 at position 691 (G>T) in intron 2.

BACKGROUND:Despite their synovial enrichment, regulatory T cells (Treg) fail to alleviate the joint inflammation in rheumatoid arthritis (RA). This indicates their functional impairment in the synovial milieu of RA patients. RESULTS:Here, we demonstrate that a deficit in the PD-1 pathway incapacitates the synovial Treg cells, and engaging programmed cell death protein-1 (PD-1) restores their suppressive function (interleukin 10, transforming growth factor beta secretion), which in turn suppresses the synovial inflammatory T cells (IFN-γ+, IL-17+ TNF-α+). We also showed that a deficit in programmed death ligand-1 expression on RA synovial macrophages contributes to impaired Treg cell function. CONCLUSION:Rejuvenating synovial Treg cell function via PD-1 engagement may be a potential strategy to ameliorate the synovial inflammation in RA patients.

HLA-C*18:06 was identified by a single nucleotide (G>A) substitution at position 275 in HLA-C*18:02.

The function of CD5 protein in T cells is well documented, but regulation of its surface-level expression has yet to be fully understood. However, variation in its surface expression is associated with various immunopathological conditions and haematological malignancies. Briefly, expression of an alternate exon E1B of a human endogenous retroviruses (HERV) origin directly downregulates the conventional transcript variant (E1A), as its expression leads to the retention of the resultant protein at the intracellular level (cCD5). A separate promoter governs the expression of E1B and may be influenced by different transcription factors. Hence, we performed in silico transcription factor binding site (TFBS) analysis of the 3kb upstream region from TSS of exon E1B and found five putative DREs (Dioxin Response elements) with good similarity scores. Further, we observed the upregulation in E1B expression after the exposure of BaP (a dioxin) and the reduction of E1A expression and their respective protein, i.e. sCD5 and cCD5. The binding of AHR at the predicted DRE sites was confirmed by ChIP qPCR and AHR specific inhibitor and gene silencing studies suggested the involvement of AHR in exonal switch. This study indicates that the polycyclic aromatic hydrocarbon decreases the sCD5 expression by upregulating alternative exon expression, which may adversely affect the overall T cell functions.

Visceral leishmaniasis (VL) is a disseminated protozoan infection of the lymphoreticular system. The disease manifestation appears owing to a severe defect in the immune system of the host. Understanding the immune status (especially IL-17) and their cross-regulation in light of Treg dominant suppressive milieu is imperative in visceral leishmaniasis patients. The present study was carried out in peripheral blood samples of thirty-four VL patients. We observed a significantly low percentage frequency of IL-17A+CD4+T cells and IL-17RA expression on monocytes; in contrast significantly higher percentage frequency of activated T cells, Treg cells and IL-10RA expression was observed on T cell subsets and monocytes of VL patients. Further, the activated T cell frequency positively correlated with Treg cell frequency while negatively correlated with T effector cells frequency. Furthermore, the rescue of IL-17A+CD4 T cells was observed in absence of Treg cells and the blocking of IL-10 and TGF-β in vitro. Moreover, suppressive cytokines down-regulate IL-17RA expression on monocytes. Our results suggest that Treg cells possibly play a dominant role in dampening the effector immune response; abrogation of Treg milieu may help in the significant rescue of protective T cell response that may help in immune restoration among visceral leishmaniasis patients.

The novel HLA-A allele HLA-A*02:01:209 sequence identified in a solid organ recipient.

We report the results of careful astrometric measurements of the cannonball pulsar J0002+6216 carried out over 3 yr using the High Sensitivity Array. We significantly refine the proper motion to μ = 35.3 ± 0.6 mas yr −1 and place new constraints on the distance, with the overall effect of lowering the velocity and increasing the inferred age to 47.60 ± 0.80 kyr. Although the pulsar is brought more in line with the standard natal kick distribution, this new velocity has implications for the morphology of the pulsar wind nebula that surrounds it, the density of the interstellar medium through which it travels, and the age of the supernova remnant (CTB 1) from which it originates.

We present X-ray and radio observations of the recently-discovered bow shock pulsar wind nebula associated with PSR J0002+6216, characterizing the PWN morphology, which was unresolved in previous studies. The multi-frequency, multi-epoch Very Large Array radio observations reveal a cometary tail trailing the pulsar and extending up to 5.3', with multiple kinks along the emission. The presented radio continuum images from multi-configuration broadband VLA observations are one of the first results from the application of multi-term multi-frequency synthesis deconvolution in combination with the awproject gridder implemented in the Common Astronomy Software Applications package (CASA). The X-ray emission observed with Chandra extends to only 21”, fades quickly, and has some hot spots present along the extended radio emission. These kinks could indicate the presence of density variation in the local ISM or turbulence. The bow shock standoff distance estimates a small bow shock region with a size 0.003-0.009 pc, consistent with the pulsar spin-down power of Edot=1.51x10^35 ergs/s estimated from timing. The high-resolution radio image reveals the presence of an asymmetry in the bow shock region which is also present in the X-ray image. The broadband radio image shows an unusually steep spectrum along with a flat-spectrum sheath, which could indicate varying opacity or energy injection into the region. Spatially-resolved X-ray spectra provide marginal evidence of synchrotron cooling along the extended tail. Our analysis of the X-ray data also shows that this pulsar has a low spin-down power and one of the lowest X-ray efficiencies observed in these objects.

Background: Acquired aplastic anemia is an autoimmune disease in which auto-aggressive T cells destroy hematopoietic progenitors. T-cell differentiation is controlled by transcription factors that interact with NOTCH-1, which influences the respective T-cell lineages. Notch signaling also regulates the BM microenvironment. The present study aimed to assess the gene expressions of NOTCH-1 and T helper cell transcription factors in the acquired aplastic anemia patients. Methods: Using quantitative real-time PCR, we studied the mRNA expression level for NOTCH-1 , its ligands ( DLL-1 and JAG-1 ), and T helper cell transcription factors (T T-BET, , GATA-3, , and ROR-gamma t) ) in both PB and BM of aAA patients and healthy controls. Further, patients of aplastic anemia were stratified by their disease severity as per the standard criteria. Results: The mRNA expression level of NOTCH-1 , T-BET, , GATA-3, , and ROR-gamma T genes increased in aAA patients compared to healthy controls. There was no significant difference in the mRNA expression of Notch ligands between patients and controls. The mRNA expression level of the above-mentioned genes was found to be higher in SAA and VSAA than NSAA patients. In addition, NOTCH-1 and T helper cell-specific transcription factors enhanced in aAA. We also observed a significant correlation between the genes and hematological parameters in patients. Conclusion: The interaction between NOTCH-1, T-BET, GATA-3, , and ROR-gamma T might lead to the activation, proliferation, and polarization of T helper cells and subsequent BM destruction. The mRNA expression levels of genes varied with disease severity, which may contribute to pathogenesis of aAA. DOI: 10.61186/ibj.3754

The full-length genomic sequence of the HLA-DRB1*13:129 allele was identified in a donor of Gujarati population.

The full length sequence of HLA-B*15:01:02 and HLA-C*08:72:01 are reported.

The full-length genomic sequence of the HLA-A*01:109 allele identified in a solid organ donor.

The novel HLA‐A allele HLA‐A*02:01:209 sequence identified in a solid organ recipient.

The extended genomic sequences of HLA-DRB1*14:04:07 and -DRB1*15:53 alleles were identified in the Gujarati individuals.

Efforts are underway to use high-precision timing of pulsars in order to detect low-frequency gravitational waves. A limit to this technique is the timing noise generated by dispersion in the plasma along the line of sight to the pulsar, including the solar wind. The effects due to the solar wind vary with time, influenced by the change in solar activity on different time scales, ranging up to ∼ 11 years for a solar cycle. The solar wind contribution depends strongly on the angle between the pulsar line of sight and the solar disk, and is a dominant effect at small separations. Although solar wind models to mitigate these effects do exist, they do not account for all the effects of the solar wind and its temporal changes. Since low-frequency pulsar observations are most sensitive to these dispersive delays, they are most suited to test the efficacy of these models and identify alternative approaches. Here, we investigate the efficacy of some solar wind models commonly used in pulsar timing using long-term, high-cadence data on 6 pulsars taken with the Long Wavelength Array, and compare them with an operational solar wind model. Our results show that stationary models of the solar wind correction are insufficient to achieve the timing noise desired by pulsar timing experiments, and we need to use non-stationary models, which are informed by other solar wind observations, to obtain accurate timing residuals.

The novel HLA-B*15:633 allele was identified in an Indian individual.