Immunology Status of Patients During Kidney Transplant.

OBJECTIVES: The immunology status of a patient has a crucial role in kidney transplant. We investigated the effectiveness of a desensitization protocol, guided by the immunology status of patients, for kidney transplant candidates. MATERIALS AND METHODS: Antibody screening for human leukocyte antigens was conducted with the Luminex single-antigen microsphere bead assay method for 34 patients from June 2021 to June 2022. Donor human leukocyte antigen genotypes at 8 loci (A*, B*, С*, DRB1*, DQA1*, DQB1*, DPA1*, and DPB1*) were determined, to correlate the specificities of recipient human leukocyte antigen antibodies with donor antigens and identify unacceptable donor antigen combinations. Specialized immunology studies measured panel reactive antibody levels and human leukocyte antigen class I and class II antibodies. A crossmatch compatibility test using complementdependent cytotoxicity was conducted. RESULTS: Of the 34 patients, 10 completed all 3 stages of the desensitization therapy. Most patients experienced decreased sensitization to human leukocyte antigen class I and class II antibodies. Two patients achieved complete clearance of A1 and DQ5 antibodies, respectively, whereas 1 patient exhibited an increase in donor-specific antibody mean fluorescence intensity. Prior to desensitization therapy, the crossmatch compatibility test yielded positive results with T and B lymphocytes. After completing the therapy, the crossmatch test showed negative results in 4 cases with T lymphocytes and positive results with B lymphocytes. Plasmapheresis sessions effectively reduced circulating antibodies. However, the combination of rituximab and plasmapheresis alone did not achieve a negative crossmatch test required for kidney transplant. CONCLUSIONS: It is crucial to assess the reduction of donor-specific antibody quantity, considering both the percentage and the mean fluorescence intensity. To avoid false-positive results in crossmatch analysis, drug half-life must be considered. Laboratories should have various crossmatch techniques, such as flow cytometry and single-antigen microsphere bead assay technology, available for research and urgent cases that require crossmatch analysis.

Total serum IgA levels and HLA-DQB1*02:01 allelic status.

Immunoglobulin A Deficiency (IgAD) is the most common primary immunodeficiency and is significantly associated with Celiac Disease (CD), which recognizes a specific background of human leukocyte antigens (HLA) predisposition (including HLA-DQB1*02:01 allele). A number of studies investigated the role of HLA in IgAD etiopathogenesis: HLA-DQB1*02 alleles are included in the main haplotypes linked to this primary immunodeficiency. In this preliminary study, we investigated the potential impact of HLA-DQB1*02:01 allelic status on total serum IgA levels: 108 serum samples from the bone marrow donors' registry were analyzed for total IgA concentration with respect to the HLA-DQB1*02:01 status. Although total serum IgA levels between HLA-DQB1*02:01 carriers and HLA-DQB1*02:01 negative donors were not different, we observed a statistically significant difference (p=0.0118) in total serum IgA levels among donors with low IgA concentration (<80mg/dL) in the sub-analysis between HLA-DQB1*02:01 positive group (including both homozygous and heterozygous carriers) compared to HLA-DQB1*02:01 negative donors. Our results might suggest a role of HLA-DQB1*02:01 allelic variant in the determination of total serum IgA levels, at least in patients affected with IgA deficiency and/or otherwise predisposed to it; however, larger and more standardized studies are needed to confirm this speculation.

Diversity of HLA-A, -B, -C, -DRB1, and -DQB1 alleles and haplotypes in Kazakhstani Tatar population and genetic relatedness to other populations.

BACKGROUND: Kazakhstan is a transcontinental former Soviet Union republic whose present-day population comprises more than 100 ethnic groups. Insofar as Human Leukocyte Antigen (HLA) genotyping is useful for anthropological studies, data on the HLA profile of Kazakhstani Tatars are lacking. OBJECTIVE: We extend our earlier findings on the unique HLA profile of distinct Kazakhstani populations by examining HLA class I and class II loci in Kazakhstani (Volga) Tatar minority population and its relatedness to those of bordering and worldwide communities. METHODS: HLA class I and class II genotypes of the Kazakhstan Tatar minority were analyzed by PCR-SSP and were compared to neighboring populations using Neighbor-Joining (NJ) trees and standard genetic distances (SGD) analysis. RESULTS: In total, 132 HLA alleles were identified in a sample of 103 Kazakhstani Tatars, of which HLA-A*02:01 (20.1 %), -B*07:02 (12.1 %), -C*07:02 (12.7 %), -DRB1*07:01 (18.1 %), and -DQB1*02:01 (19.6 %) were the most frequent. The most frequent two-locus haplotypes were B*07:02 âˆ¼ C*07:02 (10.6 %) B*07:02 âˆ¼ DRB1*15:01 (06.1 %), B*07:02 âˆ¼ DQB1*06:02 (07.1 %), and DRB1*15:01 âˆ¼ DQB1*06:02 (11.6 %). CONCLUSIONS: Considering historical data, the close relatedness of Kazakhstani Tatars to European Russians (including Russian Tatars) suggests that Kazakhstani Tatars may be Russian Tatars, who originated from the Volga region, following their massive migrations to central Asia.

HLA allele and haplotype frequencies in Kazakhstani Russians and their relationship with other populations.

HLA class I and class II genotypes from 947 Kazakhstani individuals of Russian origin were analyzed for investigating their most likely origin. The results were compared with similar data from other Russians (East and West), and also Worldwide populations, using standard genetic distances, neighbor-joining dendrograms, correspondence and haplotype analysis. Of the five HLA loci analyzed (HLA-A, HLA-C, HLA-B, HLA-DRB1, and HLA-DQB1) genotyped, 216 HLA alleles were identified. The most frequent alleles were A*02:01 (26.5%), B*07:02 (11.1%), C*04:01 (13.5%) and C*06:02 (12.1%), DRB1*07:01 (13.8%) and DRB1*15:01 (12.2%), and DQB1*03:01 (19.7%). Significant linkage disequilibrium was noted between all HLA pairs. DRB1*15:01 ~ DQB1*06:02 (10.5%), B*07:02 ~ C*07:02 (10.0%), B*07:02 ~ DRB1*15:01 (6.3%), and A*01:01 ~ B*08:01 (4.5%) were the most frequent two-locus haplotypes identified. Subsequent analyses showed that Kazakhstani Russians were closely related to West Russia-residing populations (Northwest Slavic, Vologda, Chelyabinsk, Moscow), East Europeans (Belarus Brest, Ukraine, Poland) and Scandinavians (Swedish, Finns), but distinct from East Russia-residing populations (Tuvians, Siberians from Chukotka, Kamchatka, and Ulchi) and East Mediterraneans (Levantines, Turks, North Macedonians, Albanians), and East Asians (Koreans, Japanese, Taiwanese, Mongolians). These results are in accordance with historical data indicating that the Russians of central Asia originate mainly from European Russia during the migratory flow of 18th and 19th centuries.

Distribution of HLA-A, -C, -B, -DRB1, and -DQB1 polymorphisms in the Korean minority in Kazakhstan, and relatedness to neighboring and distant populations.

BACKGROUND: Among the 125 ethnicities and linguistic groups in Kazakhstan, Koreans represent the eighth minority numerically. HLA class I and class II allele frequencies and extended haplotypes were studied for the first time and were compared to related and distant populations worldwide. METHODS: HLA class I (A, B, C) and class II (DRB1, DQB1) profile was investigated in Kazakhstani Koreans, and were compared to other populations using standard genetic distances (SGD), neighbor-joining dendrograms, correspondence, and haplotype analysis. RESULTS: One hundred and thirty-one HLA alleles were identified in Koreans living in Kazakhstan, with A*02:01 (23.08%), B*35:01 (8.24%), C*01:02 (15.38%), DRB1*08:03 (9.89%), and DQB1*03:01 (21.98%) being the most frequent alleles. A*03:01 âˆ¼ B*07:02 (3.85%), B*08:01 âˆ¼ DRB1*03:01 (3.85%), B*07:02 âˆ¼ C*07:02 (7.14%), and DRB1*08:03 âˆ¼ DQB1*06:01 (9.34%) were the most frequent two-locus haplotypes, while A*02:01 âˆ¼ B*18:01 âˆ¼ C*07:01 âˆ¼ DRB1*11:04 âˆ¼ DQB1*03:01 and A*33:03 âˆ¼ B*44:03 âˆ¼ C*14:03 âˆ¼ DRB1*13:02 âˆ¼ DQB1*06:04 (2.2% each) were the most frequent five-locus haplotypes. CONCLUSION: Korean minority in Kazakhstan was closely related to East Asians, including Mongolians (SGD, 0.044), Tuvans (East Siberia; SGD, 0.081), Burayts (Siberia; SGD, 0.094), but distant from East Mediterranean such as Lebanese (SGD, 0.367), Greek (SGD, 0.377), and Saudi (SGD, 0.414), and most Siberians (SGD, 0.473-0.699). This relatedness could be mainly attributed to massive migration of Koryo Saram to Kazakhstan in the 20th century.

Origin of the Ukrainian minority of Kazakhstan as inferred from HLA-A, -B, -C, -DRB1, and -DQB1 alleles and haplotypes distribution.

The present-day population of Kazakhstan comprises more than 100 ethnic and linguistic groups, of which Ukrainians rates numerically as the fourth, following native Kazakhs, Russians, and Uzbeks. We investigated the HLA profile of Kazakhstani Ukrainians and compared them with those of other populations by applying genetic distances, correspondence analysis, admixture, and haplotype examination. Of the 128 HLA alleles identified, A*02:01 (28.64%), B*07:02 (9.71%), B*13:02 (9.71%), C*06:02 (15.05%), DRB1*07:01 (15.20%), and DQB1*03:01 (24.76%) were the utmost common alleles. The most common 2-locus haplotypes identified were A*02:01 ~ B*13:02 (6.66%), B*13:02 ~ DRB1*07:01 (6.57%), B*13:02 ~ C*06:02 (10.10%), and DRB1*01:01 ~ DQB1*05:01 (12.12%), while A*02:01 ~ B*13:02 ~ C*06:02 ~ DRB1*07:01 ~ DQB1*02:01 were the most frequent five-locus haplotype (4.04%) in Kazakhstani Ukrainians. Comparative analysis revealed that Ukrainians of Kazakhstan are closely related to Eastern Europeans (included Ukrainians), and European Russians, but distant from Asian populations. This supports the historical notion that Kazakhstani Ukrainians originated from Ukraine, following their massive migrations to central Asia in the 18th-20th centuries.

HLA-B*51 allelic and carrier frequency in Kazakhstan: insights into Behçet's disease prevalence in Central Asia.

Behçet's disease (BD) is a systemic vasculitis whose prevalence varies according to the ethnicity. HLA-B*51 is a well-known genetic factor predisposing to BD: populations with higher HLA-B*51 allelic frequencies are also those with a greater disease prevalence, as occurs in the Silk Road countries. However, the BD prevalence is unknown in many countries, including Kazakhstan and, in general, Central Asia, despite the location on or near the Silk Road. Due to the lack of clinical studies from this area, we analyzed the bone marrow donors registry in Kazakhstan, in order to assess the HLA-B*51 allelic and carrier frequencies, which resulted to be 8.14 and 15.28%, respectively. Through a comparison with the same parameters in other countries (by performing a data search in the medical literature and in the Allele Frequency Net Database), we might speculate a BD prevalence in Kazakhstan of 10-15/100.000 at least. This result should prompt a greater clinical consideration of this disease in Central Asia, as well as the publication of clinical data from this geographic area.

Distribution of HLA Class I and Class II alleles and haplotypes in German and Uzbek minorities in Kazakhstan, and relationship to other populations.

HLA profiles of German and Uzbek minorities in Kazakhstan were analyzed and were compared with other populations. In total, 107 and 119 HLA alleles were identified in Germans and Uzbeks, respectively. A*02:01 (25.49%), B*07:02 (9.80%), B*08:01 (9.80%), C*07:02 (13.46%), DRB1*07:01 (21.57%), and DQB1*03:01 (25%) were frequent among Germans, while A*02:01 (17.86%), B*07:02 (8.33%), C*04:01 (15%), DRB1*07:01 (13.09%), and DQB1*03:01 (20%) were common alleles in Uzbeks. A*03:01 ~ B*07:02 ~ C*07:02 ~ DRB1*15:01 ~ DQB1*06:02 (6%) and A*24:02 ~ B*38:01 ~ C*12:03 ~ DRB1*14:01 ~ DQB1*05:03 (3.75%) were the most frequent five-locus haplotypes in Germans and Uzbeks, respectively. Germans of Kazakhstan are genetically related to European Russians, Germans and Eastern Europeans, suggesting their European Russia (Volga Region) origin following their 19th century migration to central Asia. Uzbeks, likely indigenous, were genetically close to Eastern Russians, Europeans, and Asians.

Genetic predisposition to celiac disease in Kazakhstan: Potential impact on the clinical practice in Central Asia.

BACKGROUND: Celiac disease (CD) is a systemic immune-mediated disorder developing in HLA genetically predisposed individuals carrying HLA-DQ2 and/or HLA-DQ8 molecules. Recent evidences supported a predominant importance of HLA-DQB1 locus and, in particular, HLA-DQB1*02 alleles. This diagnosis is poorly considered in Kazakhstan, because of the assumption that CD is not prevalent in this population. OBJECTIVE: To demonstrate that the genetic predisposition to CD in Kazakhstan is not negligible and is actually comparable to Western populations. METHODS: Through the analysis of HLA-DQ genotypes of healthy bone marrow donors from Kazakhstan's national registry, we estimated the HLA-related genetic predisposition to CD in the country. RESULTS: We demonstrated that the frequency of CD-related HLA-DQB1 alleles and, as a consequence, of predisposed individuals to CD in Kazakhstan is significant and comparable to countries with the highest disease prevalence. CONCLUSION: Considering the dietary style in Kazakhstan, including wheat as a staple food, these results provided a preliminary background of knowledge to expect a significant CD prevalence in Kazakhstan and Central Asia by implementing appropriate and cost-effective diagnostic strategies.