MICA Gene Research Articles

MICA and NKG2D gene polymorphisms influence graft survival, and response to therapy in kidney transplantation

MICA and NKG2D gene polymorphisms influence graft survival, and response to therapy in kidney transplantation

Soluble MICA concentrations and genetic variability of MICA and its NKG2D receptor as factors affecting Graft-versus-Host Disease development after allogeneic haematopoietic stem cell transplantation

Despite new treatment strategies, graft-versus-host disease (GvHD) remains a formidable complication after allogeneic hematopoietic stem cell transplantation (HSCT). This study aimed to investigate the impact of polymorphisms and expression of MICA and NKG2D receptor on the development of GvHD in allogeneic HSCT recipients. Soluble MICA (sMICA) concentration was measured in serum collected 30 days after transplantation and the genetic variability of MICA and NKG2D genes was evaluated. The frequency of NKG2D+NK cells was determined by flow cytometry before and (21, 30, 60 and 90 days) after transplantation. Recipients with acute GvHD grades II-IV carried the NKG2D rs1049174 C allele more frequently than controls or patients with no or mild disease. Patients with chronic GvHD had higher frequency of NKG2D expressing NK cells posttransplant, reflecting increased activity of their NK cells. Although no direct relationship between MICA SNPs and GvHD were observed, the presence of MICA rs1051792 GG genotype correlated with elevated sMICA levels and increased serum level of sMICA was associated with higher risk of chronic GvHD. Our findings suggest that sMICA concentration may serve as a potential biomarker for chronic GvHD and emphasize the impact of genetic variability of NKG2D and its surface expression on the HSCT outcome.

A multi-ethnic reference panel to impute HLA classical and non-classical class I alleles in admixed samples: Testing imputation accuracy in an admixed sample from Brazil.

The MHC class I region contains crucial genes for the innate and adaptive immune response, playing a key role in susceptibility to many autoimmune and infectious diseases. Genome-wide association studies have identified numerous disease-associated SNPs within this region. However, these associations do not fully capture the immune-biological relevance of specific HLA alleles. HLA imputation techniques may leverage available SNP arrays by predicting allele genotypes based on the linkage disequilibrium between SNPs and specific HLA alleles. Successful imputation requires diverse and large reference panels, especially for admixed populations. This study employed a bioinformatics approach to call SNPs and HLA alleles in multi-ethnic samples from the 1000 genomes (1KG) dataset and admixed individuals from Brazil (SABE), utilising 30X whole-genome sequencing data. Using HIBAG, we created three reference panels: 1KG (n = 2504), SABE (n = 1171), and the full model (n = 3675) encompassing all samples. In extensive cross-validation of these reference panels, the multi-ethnic 1KG reference exhibited overall superior performance than the reference with only Brazilian samples. However, the best results were achieved with the full model. Additionally, we expanded the scope of imputation by developing reference panels for non-classical, MICA, MICB and HLA-H genes, previously unavailable for multi-ethnic populations. Validation in an independent Brazilian dataset showcased the superiority of our reference panels over the Michigan Imputation Server, particularly in predicting HLA-B alleles among Brazilians. Our investigations underscored the need to enhance or adapt reference panels to encompass the target population's genetic diversity, emphasising the significance of multiethnic references for accurate imputation across different populations.

Impact of donor NKG2D and MICA gene polymorphism on clinical outcomes of adult and paediatric allogeneic cord blood transplantation for malignant diseases.

NKG2D is an activating receptor expressed by natural killer (NK) and CD8+ T cells and activation intensity varies by NKG2D expression level or nature of its ligand. An NKG2D gene polymorphism determines high (HNK1) or low (LNK1) expression. MICA is the most polymorphic NKG2D ligand and stronger effector cell activation associates with methionine rather than valine at residue 129. We investigated correlation between cord blood (CB) NKG2D and MICA genotypes and haematopoietic stem cell (HSC) transplant outcome. We retrospectively studied 267 CB HSC recipients (178 adult and 87 paediatric) who underwent transplant for malignant disease between 2007 and 2018, analysing CB graft DNA for NKG2D and MICA polymorphisms using Sanger sequencing. Multivariate analysis was used to correlate these results with transplant outcomes. In adult patients, LNK1 homozygous CB significantly improved 60-day neutrophil engraftment (hazard ratio (HR) 0.6; 95% confidence interval (CI) 0.4-0.9; p = .003). In paediatrics, HNK1 homozygous CB improved 60-day engraftment (HR 0.4; 95% CI 0.2-0.7; p = .003), as did MICA-129 methionine+ CB grafts (HR 1.7 95% CI 1.1-2.6; p = .02). CB NKG2D and MICA genotypes potentially improve CB HSC engraftment. However, results contrast between adult and paediatric recipients and may reflect transplant procedure disparities between cohorts.

Functional MICA Variants Are Differentially Associated with Immune-Mediated Inflammatory Diseases.

As the principal ligand for NKG2D, MICA elicits the recruitment of subsets of T cells and NK cells in innate immunity. MICA gene variants greatly impact the functionality and expression of MICA in humans. The current study evaluated whether MICA polymorphisms distinctively influence the pathogenesis of psoriasis (PSO), rheumatoid arthritis (RA), and systemic lupus erythematosus (SLE) in Taiwanese subjects. The distributions of MICA alleles and levels of serum soluble NKG2D were compared between healthy controls and patients with PSO, RA, and SLE, respectively. The binding capacities and cell surface densities of MICA alleles were assessed by utilizing stable cell lines expressing four prominent Taiwanese MICA alleles. Our data revealed that MICA*010 was significantly associated with risks for PSO and RA (PFDR = 1.93 × 10-15 and 0.00112, respectively), while MICA*045 was significantly associated with predisposition to SLE (PFDR = 0.0002). On the other hand, MICA*002 was associated with protection against RA development (PFDR = 4.16 × 10-6), while MICA*009 was associated with a low risk for PSO (PFDR = 0.0058). MICA*002 exhibited the highest binding affinity for NKG2D compared to the other MICA alleles. Serum concentrations of soluble MICA were significantly elevated in SLE patients compared to healthy controls (p = 0.01). The lack of cell surface expression of the MICA*010 was caused by its entrapment in the endoplasmic reticulum. As a prevalent risk factor for PSO and RA, MICA*010 is deficient in cell surface expression and is unable to interact with NKG2D. Our study suggests that MICA alleles distinctively contribute to the pathogenesis of PSO, RA, and SLE in Taiwanese people.

Novel Association of KLRC4-KLRK1 Gene Polymorphisms with Susceptibility and Progression of Antithyroid Drug-Induced Agranulocytosis.

Antithyroid drug (ATD)-induced agranulocytosis (TIA) is the most serious adverse effect during ATD treatment of Graves' disease (GD). Previously, the MICA gene was reported to be associated with TIA. MICA protein is an important ligand for the NKG2D protein, which is encoded by the KLRK1 gene and KLRC4-KLRK1 read-through transcription. This study further investigated the association between KLRC4-KLRK1 gene polymorphisms and susceptibility to TIA. Twenty-eight candidate single nucleotide polymorphisms (SNPs) on KLRC4-KLRK1 read-through transcription were evaluated by the iPLEX MassARRAY system in 209 GD control patients and 38 TIA cases. A significant association of rs2734565 polymorphism with TIA was found (p=0.02, OR=1.80, 95% CI=1.09-2.96). The haplotype C-A-A-C-G, including rs2734565-C, was associated with a significantly higher risk of TIA (p=4.79E-09, OR=8.361, 95% CI=3.737-18.707). In addition, the interval time from hyperthyroidism to agranulocytosis onset was shorter in patients carrying the rs2734565-C allele than in non-carrying groups (45.00 (14.00-6570.00) d vs. 1080.00 (30.00-3600.00) d, p=0.046), and the interval from ATD treatment to agranulocytosis onset was also shorter in patients carrying rs2734565-C allele (29.00 (13.00-75.00) d vs. 57.50 (21.00-240.00) d, p=0.023). The findings suggest that the KLRC4-KLRK1 gene polymorphism is associated with susceptibility and progression of ATD-induced agranulocytosis. Patients carrying the rs2734565-C allele had a higher susceptibility and faster onset time of TIA.

High population frequencies of MICA copy number variations originate from independent recombination events.

MICA is a stress-induced ligand of the NKG2D receptor that stimulates NK and T cell responses and was identified as a key determinant of anti-tumor immunity. The MICA gene is located inside the MHC complex and is in strong linkage disequilibrium with HLA-B. While an HLA-B*48-linked MICA deletion-haplotype was previously described in Asian populations, little is known about other MICA copy number variations. Here, we report the genotyping of more than two million individuals revealing high frequencies of MICA duplications (1%) and MICA deletions (0.4%). Their prevalence differs between ethnic groups and can rise to 2.8% (Croatia) and 9.2% (Mexico), respectively. Targeted sequencing of more than 70 samples indicates that these copy number variations originate from independent nonallelic homologous recombination events between segmental duplications upstream of MICA and MICB. Overall, our data warrant further investigation of disease associations and consideration of MICA copy number data in oncological study protocols.

Association of MICA and NKG2D genetic variants with disease susceptibility and outcome of anti-TNF therapy in patients with axial spondyloarthritis.

The disruption of the NKG2D-MICA axis can induce an enhanced immune response and promote autoimmune processes during axial spondyloarthritis (axSpA) pathogenesis. We aimed to investigate potential relationships between selected single nucleotide polymorphisms within the MICA and NKG2D genes and disease susceptibility and clinical parameters in axSpA patients treated with TNF inhibitors. Genotyping of MICA rs1051792 and NKG2D rs1154831, rs1049174, and rs2255336 was performed in 163 axSpA patients and 234 healthy controls using a real-time PCR method. MICA rs1051792 A allele was more common in patients than in controls (p<0.0001). Patients with the AA genotype showed greater disease activity score (BASDAI) after three (p=4×10-4) and six (p=0.032) months of treatment compared to G carriers. After three months of therapy with anti-TNFs, the MICA AA homozygosity occurred more often in non-responsive or moderately responsive patients than good responders with the same genotype (p=1×10-4). Additionally, patients bearing the NKG2D rs1154831 CC genotype demonstrated lower BASDAI scores (p=0.035) and were significantly more common among subjects with a good outcome (p=0.004) after six months of treatment. These results suggest that MICA and NKG2D gene polymorphisms may be biomarkers associated with disease susceptibility and clinical outcomes after anti-TNF therapy in axSpA patients and imply a rather less favourable effect of the MICA A and NKG2D G genetic variants.

MICA and NLRP3 gene polymorphisms interact synergistically affecting the risk of ankylosing spondylitis.

Ankylosing spondylitis (AS) is an autoinflammatory disease that affects the sacroiliac joints, causing stiffness and pain in the back. MICA is a ligand of the NKG2D receptor, and an increase in its expression affects the immune response in various diseases. NLRP3 is a multiprotein complex that promotes the release of IL-1β, but its role in AS has been minimally explored. The objective of this study was to analyze the association and interaction of polymorphic variants of the MICA and NLRP3 genes in patients with AS. In this case-control study, patients with AS were included and compared with healthy controls of Mexican origin. The polymorphisms rs4349859 and rs116488202 of MICA and rs3806268 and rs10754558 of NLRP3 were genotyped using TaqMan probes. Associations were determined using logistic regression models, while interactions were analyzed by the multifactorial dimensionality reduction (MDR) method. A P value < 0.05 was considered statistically significant. The minor allele of rs4349859 (A) and rs116488202 (T) of MICA polymorphisms showed risk associations with AS (OR = 9.22, 95% CI = 4.26-20.0, P < 0.001; OR = 9.36, 95% CI = 4.17-21.0, P < 0.001), while the minor allele of the rs3806268 (A) polymorphism of NLRP3 was associated with protection (OR = 0.55, 95% CI = 0.33-0.91, P = 0.019). MDR analysis revealed synergistic interactions between the MICA and NLRP3 polymorphisms (P = 0.012). In addition, high- and low-risk genotypes were identified among these variants. The study findings suggest that the MICA rs4349859 A allele and rs116488202 T allele are associated with AS risk. An interaction between MICA and NLRP3 was observed which could increase the genetic risk in AS.

Exploration of the role of NKG2D ligands MICA and MICB in JAK2 V617F-positive myeloproliferative neoplasms.

JAK2 V617F-driven myeloproliferative neoplasms (MPNs) can escape immune surveillance through PD-L1 up-regulation and HLA class I pathway down-regulation. To complement these data we assessed the role of major histocompatibility complex class I-related genes (MICA and MICB) in JAK2 V617F+ MPNs. Using high resolution genotyping we identified two protective alleles, MICA*008:01 and MICA*016. MPN patients had significantly higher levels of soluble sMICA molecules. Peripheral blood JAK2 V617F+ granulocytes had higher surface expression of MICB but did not differ in the amount of MICA and MICB transcripts from normal granulocytes. MICA and MICB genes were significantly down-regulated in JAK2 V617F+ CD34+ cells from primary myelofibrosis patients in comparison to normal CD34+ hematopoietic stem cells. These data suggest minor but significant role of MICA and MICB genes in the pathogenesis of MPNs. It is also possible that MICA targeting approaches could be of clinical benefit for some of those patients.

Gene variations related to the hepatocellular carcinoma: Results from a field synopsis and Bayesian revaluation

Hepatocellular carcinoma (HCC) is considered as the second cause of cancer-related deaths worldwide. Genetic variations are associated with HCC risk, an issue that has been the subject of several meta-analyses. However, meta-analyses have an important limitation on the likelihood of false positive data. Henceforth, this study aimed to assess the level of noteworthiness in the meta-analyses by means of a Bayesian approach. A systematic search was performed for meta-analyses with associations between gene polymorphisms and HCC. The calculations for the False-Positive Rate Probability (FPRP) and the Bayesian False Discovery Probability (BFDP) were performed to assess the noteworthiness with a statistical power of 1.2 and 1.5 of Odds Ratio at a prior probability of 10−3 and 10−5. The quality of studies was evaluated by the Venice criteria. As additional analyses, the gene-gene and protein–protein networks were designed for these genes and products. As results, we found 33 meta-analytic studies on 45 polymorphisms occurring in 35 genes. A total of 1,280 values for FPRP and BFDP were obtained. Seventy-five for FPRP (5.86%) and 95 for BFDP (14.79%) were noteworthy. In conclusion, the polymorphisms in CCND1, CTLA4, EGF, IL6, IL12A, KIF1B, MDM2, MICA, miR-499, MTHFR, PNPLA3, STAT4, TM6SF2, and XPD genes were considered as noteworthy biomarkers for HCC risk.

Targeted plasma proteomics identifies MICA and IL1R1 proteins associated with HIV-1 reservoir size

HIV-1 reservoir shows high variability in size and activity among virally suppressed individuals. Differences in the size of the viral reservoir may relate to differences in plasma protein concentrations. We tested whether plasma protein expression levels are associated with levels of cell-associated (CA) HIV-1 DNA and RNA in 211 virally suppressed people living with HIV (PLHIV). Plasma concentrations of FOLR1, IL1R1, MICA, and FETUB showed a positive association with CA HIV-1 RNA and DNA. Moreover, SNPs in close proximity to IL1R1 and MICA genes were found to influence the levels of CA HIV-1 RNA and DNA. We found a difference in mRNA expression of the MICA gene in homozygotes carrying the rs9348866-A allele compared to the ones carrying the G allele (p<0.005). Overall, our findings pinpoint plasma proteins that could serve as potential targets for therapeutic interventions to lower or even eradicate cells containing CA HIV-1 RNA and DNA in PLHIV.

MICA and MICB allele assortment in Finland.

Genetic variation in the MICA and MICB genes located within the major histocompatibility complex region has been reported to be associated with transplantation outcome and susceptibility to autoimmune diseases and infections. Only limited data of polymorphism in these genes in different populations are available. We here report allelic variation at 2-field resolution and the haplotypes of the MICA and MICB genes in Finland (n= 1032 individuals), a north European population with historical bottleneck and founder effects. Altogether 24 MICA and 18 MICB alleles were found, forming 70 estimated MICA-MICB haplotypes. As compared to other populations frequency differences were found, for example, MICA*010:01 was found to be at an allele frequency of 0.133 in Finland which is higher than in other European populations (0.021-0.077), but close to Asian populations (0.151-0.220). Three novel alleles with amino acid change are described. The results demonstrate a relatively high level of polymorphism and population differences in MICA and MICB allele distribution.

Inhibition of Checkpoint Kinase 1 (CHK1) Upregulates Interferon Regulatory Factor 1 (IRF1) to Promote Apoptosis and Activate Anti-Tumor Immunity via MICA in Hepatocellular Carcinoma (HCC).

CHK1 is considered a key cell cycle checkpoint kinase in DNA damage response (DDR) pathway to communicate with several signaling pathways involved in the tumor microenvironment (TME) in numerous cancers. However, the mechanism of CHK1 signaling regulating TME in hepatocellular carcinoma (HCC) remains unclear. CHK1 expression in HCC tissue was determined by IHC staining assay. DNA damage and apoptosis in HCC cells induced by cisplatin or CHK1 inhibition were detected by WB and flow cytometry. The interaction of CHK1 and IRF1 was analyzed by single-cell RNA-sequence, WB, and immunoprecipitation assay. The mechanism of IRF1 regulating MICA was investigated by ChIP-qPCR. CHK1 expression is upregulated in human HCC tumors compared to the background liver. High CHK1 mRNA level predicts advanced tumor stage and worse prognosis. Cisplatin and CHK1 inhibition augment cellular DNA damage and apoptosis. Overexpressed CHK1 suppresses IRF1 expression through proteolysis. Furthermore, single-cell RNA-sequence analyses confirmed that MICA expression positively correlated with IRF1 in HCC cells. Immunoprecipitation assay showed the binding between CHK1 and IRF1. Cisplatin and CHK1 inhibition upregulate MICA expression through IRF1-mediated transcriptional effects. A novel specific cis-acting IRF response element was identified at -1756 bp in the MICA promoter region that bound IRF1 to induce MICA gene transcription. MICA may increase NK cell and CD8+T cell infiltration in HCC. DNA damage regulates the interaction of CHK1 and IRF1 to activate anti-tumor immunity via the IRF1-MICA pathway in HCC.

Analysis of the association between MICA gene polymorphisms and schizophrenia.

The major histocompatibility complex (MHC) has been implicated in schizophrenia. This study aimed to explore the correlation between the major histocompatibility complex class I polypeptide-related sequence A (MICA) polymorphisms and schizophrenia. A total of 220 Han schizophrenia patients, 47 Han healthy controls, 155 Li schizophrenia patients, and 48 Li controls were selected from Hainan Province, China. The diagnosis was made according to the Diagnostic and Statistical Manual of Mental Disorders, 4th edition, criteria. Sequencing-based-typing (PCR-SBT) technology was used for MICA allele typing, and the correlation analyses of MICA gene polymorphism and schizophrenia were performed. In the Han group, the three allele frequencies of MICA*002:01, MICA*A4, and MICA*A9 in the schizophrenia group were significantly higher than those in the healthy control group, and the differences were statistically significant (pc < 0.05; pc values were 0.024, 0.030, and 0.031, respectively). Yet, there was no difference in the MICA gene between the schizophrenia group and the healthy controls group in the Li population. We found MICA*002:01, MICA*A4, and MICA*A9 may be susceptibility alleles for schizophrenia in the Han population, while the MICA allele polymorphism in the Li population is not associated with schizophrenia in Chinese.

Association of MICA gene Exon-5 polymorphism in oral submucous fibrosis

The present study was conducted to explore the allele frequencies of MICA gene Exon-5 transmembrane and to measure the circulatory MICA levels in various histologic grades of patients with oral submucous fibrosis (OSF) compared to healthy individuals. We enrolled a total of 595 patients for this cross-sectional study and divided them into 2 groups: healthy controls (n=320) and patients with OSF (n=275). Further, patients with OSF were subdivided based on their histologic gradings. The genomic DNA was extracted followed by a polymerase chain reaction and genotyping using the ABI Prism DNA Sequencer (ThermoFisher Scientific, Inc., Waltham, MA, USA). Our study showed that the A5 allele of the MICA gene in the Exon-5 region conferred significant risk for patients with OSF. With reference to the histologic gradings of OSF, we found that the MICA gene conferred statistically significant risk among patients with grade III OSF. On the other hand, the A8 allele of MICA gene in the Exon-5 region conferred significant protection among the overall OSF cohort and in the grade III of histologic grade. Finally, the circulatory human MICA levels were found to have a stepwise increase from grade I toward grade III in patients with OSF. Our results suggested that the A5 allele in MICA might confer risk for the progression of OSF among the South Indian ethnic population.

Frequency and parameters of linkage disequilibrium of the two-locus &lt;i&gt;HLA-B~MICA&lt;/i&gt; haplotypes in russians from chelyabinsk region

MICA gene is located in the MHC region on chromosome 6p21.33, mapped ca. 46.4 kb centromeric to the HLA-B gene, being in strict linkage disequilibrium with MHC class I region. The sufficient polymorphism of human MICA gene and its location at the HLA region makes it a likely candidate locus for additional histocompatibility testing. The data on distribution of two-locus HLA-B~MICA haplotypes enable us to obtain information about the level of mismatches in the MICA locus when selecting suitable donor-recipient pair by convential HLA loci for unrelated hematopoietic stem cell transplantation. We have performed immunogenetic typing of 100 donors of Russian Nationality from the Register of Stem Cell Donors at Chelyabinsk Regional Blood Bank. MICA genotyping was carried out by PCR tests with sequence-specific primers at basic resolution. Typing of the classical HLA-B locus was carried out by the NGS method using MiSeq instrument using a MiSeq v2 reagent kit (Illumina). Linkage disequilibrium indices D, D`, p, and the frequency of two-locus HLA-B~MICA haplotypes were calculated using Arlequin 3.5 software. As a result of this study, the main parameters of linkage disequilibrium and the frequency of two-locus HLA-B~MICA haplotypes were established for Russians from the Chelyabinsk region. HLA-B allelic groups have been identified that form stable pairs with specific MICA allelic variants (HLA-B*B*07, B*08, B*13, B*14, B* 27, B*37, B*38, B*47, B *48, B*49, B*50, B*52, B*55, B*56, B*57). Moreover, we have revealed HLA-B allelic groups forming highly variable HLA-B~MICA haplotypes (HLA-B*15, B*18, B*35, B*39, B*40, B*41, B*44 and B*51) with increased risk of mismatch for MICA genes. These results could be used in clinical practice in order to assess probability of the donor/recipient mismatch for non-classic MICA locus when selecting potential stem cell donors for hematological patients by HLA testing of classical loci. Moreover, these data could be demanded in population genetics.

HLA class I chain-related MICA and MICB genes polymorphism in healthy individuals from the Bulgarian population

Although human leukocyte antigen (HLA) gene polymorphism has been investigated in many populations around the world, the data on MHC class I chain-related (MIC) genes are still limited. The present study is aimed to analyze the allelic polymorphism of MICA and MICB genes and haplotype associations with HLA-B locus in 132 healthy, unrelated individuals from the Bulgarian population by next generation sequencing (NGS). A total of 36 MICA and 16 MICB alleles were observed with the highest frequency detected for MICA*008:01 (17.1%) and MICB*005:02 (32.4%). Further, two and three-loci haplotype frequencies and pairwise linkage disequilibrium were estimated. Highly significant global linkage disequilibrium was found between either HLA-B and MICA and MICB genes. This is the first study on MICA and MICB allelic polymorphism, linkage disequilibrium, and haplotype polymorphism in the Bulgarian population. These results will allow for better characterization of the genetic heterogeneity of the Bulgarian population and could contribute to further analyses on MICA and MICB clinical significance.

A study of the association between long non coding RNA (ULBP1 and MICA/B) expression and preeclampsia in Egypt

BackgroundPreeclampsia is associated with excessive inflammation and increased serum monokines. Although preeclampsia pathogenesis has been connected to uterine natural killer (NK) cells, natural killer group 2, member D (NKG2D) is thought to have a role in immune response mediation. NKG2D ligands (NKG2DLs) are significantly expressed in preeclampsia, and the heterogeneity of NKG2DL expression is unclear. Aim of the studyIn current study we aimed to study the expression levels of ULBP1 and MICA/B genes in women with preeclampsia. Patients & methodsThe Medical Biochemistry and Molecular Biology Department, as well as the Gynecological Department, at Menofia University's Faculty of Medicine, conducted this research. There were 120 female in all, with 80 of them having preeclampsia (40 mild and 40 severe preeclampsia). There were 40 healthy pregnant women as control group. All were chosen from the Menofia University Hospital's, Gynecological and Obstetric Departments between May 2020 and May 2021. After all subjects have given their informed permission, full history taking, clinical examination were performed on all participants and laboratory examinations include: measurement of liver function tests (AST&ALT), renal function tests (urea, creatinine, and uric acid), complete blood count, assessment of protein in urine and calculation of gene expression of ULPB1, MICA, and MICB in placental tissue by real time q PCR method. ResultsThere was significant increase in ULPB1, MICA and MICB genes expression in cases versus control and there was significant higher level of ULPB1, MICA, and MICB in severe cases compared to mild cases. ConclusionFrom this study, it could be concluded that expression of ULPB1, MICA and MICB levels might be used as biomarkers for diagnosis and detection of severity of preeclampsia.

The MHC class I MICA gene is a histocompatibility antigen in kidney transplantation

The identity of histocompatibility loci, besides human leukocyte antigen (HLA), remains elusive. The major histocompatibility complex (MHC) class I MICA gene is a candidate histocompatibility locus. Here, we investigate its role in a French multicenter cohort of 1,356 kidney transplants. MICA mismatches were associated with decreased graft survival (hazard ratio (HR), 2.12; 95% confidence interval (CI): 1.45–3.11; P < 0.001). Both before and after transplantation anti-MICA donor-specific antibodies (DSA) were strongly associated with increased antibody-mediated rejection (ABMR) (HR, 3.79; 95% CI: 1.94–7.39; P < 0.001; HR, 9.92; 95% CI: 7.43–13.20; P < 0.001, respectively). This effect was synergetic with that of anti-HLA DSA before and after transplantation (HR, 25.68; 95% CI: 3.31–199.41; P = 0.002; HR, 82.67; 95% CI: 33.67–202.97; P < 0.001, respectively). De novo-developed anti-MICA DSA were the most harmful because they were also associated with reduced graft survival (HR, 1.29; 95% CI: 1.05–1.58; P = 0.014). Finally, the damaging effect of anti-MICA DSA on graft survival was confirmed in an independent cohort of 168 patients with ABMR (HR, 1.71; 95% CI: 1.02–2.86; P = 0.041). In conclusion, assessment of MICA matching and immunization for the identification of patients at high risk for transplant rejection and loss is warranted.