HLA-A, -C, -B, -DRB1, -DQA1, and -DQB1 Allele and Haplotype Repertoires in the Albanian Population from Kosovo.

To give new insight into the huge polymorphism of HLA system and supplement the existing data, an analysis of HLA alleles and HLA-A~C~B~DRB1~DQA1~DQB1 haplotype distribution in 124 Albanian individuals from Kosovo was performed. All samples were HLA-typed applying the polymerase chain reaction-sequence specific oligonucleotide probing (PCR-SSOP) method and all ambiguous HLA typing results were additionally confirmed by the standard PCR-Sequence Specific Primers (PCR-SSP) high-resolution protocol. Twenty-two HLA-A, 21 HLA-C, 37 HLA-B, 27 HLA-DRB1, 11 HLA-DQA1 and 14 HLA-DQB1 allele groups were detected. Sixteen out of 172 different six-locus estimated haplotypes were found at a frequency higher than 1.00% with a cumulative frequency of 28.82%. The most prevalent haplotype was found to be HLA-A*02:01~C*07:01~B*18:01~DRB1*11:04~DQA1*05:05~DQB1*03:0(5.2%).A total of 13 haplotypes were observed with higher frequency than in populations reported in HaploStats and The Allele Frequency Net Database. The proposed origin of the most frequent haplotypes reflects a basic Euro-Mediterranean background of Albanians in Kosovo. This is the first report of high-resolution HLA-A~C~B~DRB1~DQA1~DQB1 haplotype distribution among the Albanian population from Kosovo, which provides valuable anthropological data and confirms population-specific characteristics.

Susceptible and protective HLA-DR and HLA-DQ alleles for Fya alloimmunization in the Croatian population.

BACKGROUND: Alloimmunization is a known risk of transfusion therapy caused by exposure to foreign RBC antigens. However, alloimmunization is not observed in all transfused patients. Human leukocyte antigen (HLA) molecules may contribute to the recognition and presentation of foreign antigens and to the potency of immune responses that result in the production of antibodies. The aim of this study was to determine the association of HLA-DR and HLA-DQ polymorphisms with alloimunization to Fya antigen in Croatian patients. STUDY DESIGN AND METHODS: The study was conducted on 70 alloimmunized patients to Fya antigen and two control groups: 165 healthy Croatian individuals (Control 1) and 45 Fya antigen-negative nonimmunized patients exposed to Fya antigen (Control 2). Phenotype frequencies for HLA-DRB1 and HLA-DQB1 alleles were compared between the cases and control groups. RESULTS: Statistically significant differences in phenotype frequencies between cases and controls were found for DRB1*04 (odds ratios [ORs], 10.5 and 18.7 for Control 1 and Control 2, respectively), DRB1*15 (ORs, 8.0 and 6.9), and DQB1*02 alleles (ORs, 0.2 and 0.03); and DRB1*04-DQB1*03:01 (ORs, 7.9 and 17.6), DRB1*04-DQB1*03:02 (ORs, 5.5 and 7.6), DRB1*15-DQB1*06:02 (ORs, 7.3 and 5.5), DRB1*03-DQB1*02:01 (OR, 0.1), and DRB1*07-DQB1*02:02 (OR, 0.3) haplotypes. CONCLUSION: Several HLA-DRB1 and HLA-DQB1 alleles and haplotypes were proved to contribute to and protect from alloimmunization to Fya antigens. Alleles DRB1*04 and DRB1*15, as well as haplotypes DRB1*04-DQB1*03:02 and DRB1*15-DQB1*06:02 can be considered as risk factors, while allele DQB1*02 and haplotype DRB1*03-DQB1*02:01 have a protective role in Fya alloimmunization.

An intermediate-sized donor registry experience: HLA barriers in matching procedures.

The data enabling the estimation of the possibility of finding a matched unrelated donor (MUD) within a relatively short time is important for the success of hematopoietic stem cell transplantation (HSCT). In the present study, 738 unrelated Croatian patients in the program of unrelated HSCT were retrospectively analyzed for gender matching, donor origin (national or international), the distribution of HLA alleles and haplotypes, as well as for the probability of finding a 9-10/10 MUD. Almost 70% of the patients in our study group had a 10/10 MUD, while among the patients with a 9/10 MUD, a 1st field resolution level mismatched donor was selected for 55.0% of patients. The majority of pairs were HLA-A mismatched (33.8%). A comparison of HLA allele frequencies between two subgroups of patients revealed significant differences for 13 alleles. However, after p value correction, the difference in frequency remained significant only for four alleles; three HLA alleles (B*08:01, C*07:01, and DRB1*03:01) demonstrated a significantly higher frequency among patients with a 10/10 MUD (Pcorr < 0.0001, Pcorr = 0.0096, and Pcorr < 0.0001, respectively), while the B*35:08 allele was significantly more present among patients with a 9/10 MUD (Pcorr = 0.0328). The comparison of the distribution of HLA haplotypes between patients with a 10/10 MUD and patients with a 9/10 MUD showed significant differences for a number of two-locus and three-locus haplotypes, as well as for one five-locus haplotype (HLA-A*01:01~B*08:01~C*07:01~DRB1*03:01~DQB1*02:01), which was significantly more present in the group of patients with a 10/10 MUD. At least one HLA haplotype from the group of non-frequent HLA haplotypes (positions >1000) was carried by patients with a 9/10 MUD. The data obtained by the present study will contribute to a better estimation of the probability of finding a suitable 9-10/10 MUD for Croatian patients in need of HSCT.

Detection of novel HLA alleles by Next-Generation Sequencing in the Croatian population.

The introduction of Next-Generation Sequencing (NGS) methodology in the histocompatibility testing for both allo-HSCT and solid organ transplantation enables the sequencing of all HLA genes, which in turn leads to the discovery of many new HLA alleles. Over the last 3 years, we have identified 28 novel alleles (HLA-A*02:1079, A*03:01:01:112, A*11:01:01:83, A*11:01:01:87, A*24:595, A*68:01:01:15, B*07:02:01:107, B*08:01:01:67, B*08:01:01:69, B*13:02:01:25, B*15:01:82, B*15:18:08, B*18:01:01:76, B*27:02:06, B*27:05:02:34, B*40:06:01:17, B*40:517, C*04:01:01:173, C*04:477, C*05:276, C*07:01:01:130, C*12:03:80, C*12:03:01:62, DQA1*05:01:01:10, DPB1*13:01:07, DPB1*1146:01, DPB1*1456:01 and DPB1*1514:01) using the NGS method. The presented data emphasises the benefits gained by the utilisation of the NGS-based techniques in HLA genotyping but also provides new insight on the HLA polymorphism in the Croatian population.

Immunomodulatory Effect of COVID-19 on HLA-Antibody Profile in Renal Transplant Recipients.

Background/Objectives: The novel coronavirus disease 2019 (COVID-19) has led to significant morbidity and mortality among kidney transplant recipients. SARS-CoV-2 has been hypothesized to cause an unusual immunological dysregulation triggering alloimmunity and leading to graft rejection. Methods: This prospective observational cohort study assessed 321 kidney transplant recipients who had COVID-19 infection. After the infection, patients' sera were tested for the presence of anti-HLA de novo DSA and non-DSA specificities. Logistic regression analysis and a stepwise multivariable logistic regression analysis were used to analyze the independent risk factors associated with the development of antibodies, adjusting for known confounders. The variables evaluated were acute COVID-19 characteristics (i.e., presentation, and need for hospitalization), demographic characteristics (i.e., age, gender, and primary renal disease), clinical characteristics (i.e., various comorbidities), and post-COVID-19 sequelae. Results: Anti-HLA de novo DSA developed in 18.7% of patients, while anti-HLA class I and class II non-DSA antibodies developed de novo in 84 (26.3%) and 83 (25.9%) patients, respectively. The development of DSA, HLA-DQ, and HLA-DR antibodies was predicted by the history of graft rejection. Obesity appeared to be protective against the emergence of de novo DSA. De novo DSA and HLA-DR antibody formation was positively linked with intravenous immunoglobulin use, CMV-hyperimmune globulin use, and decreased doses of immunosuppression during acute infection. Better allograft function during the acute disease was a protective factor against the formation of HLA-DQ and HLA-DR antibodies. Positive predictors of de novo DSA development were graft biopsy and the reactivation of EBV after infection. Conclusions: These findings suggest that the SARS-CoV-2 virus has an immunomodulatory effect and may be associated with an increased mortality in this population.

The association between the HLA system and retinopathy development in patients with type 1 diabetes mellitus.

Duration of diabetes and chronic hyperglycemia are the most important risk factors in the pathogenesis of diabetic retinopathy (DR). However, there is increasing evidence suggesting that genetic factors may also contribute to its development. The aim of this study was to determine the role of the HLA system in the development of DR in patients with type 1 diabetes mellitus. Class II genes (DRB1, DQB1) were typed using the PCR-SSP method. Based on the fundus examination the patients were divided into two groups: one group with no or mild nonproliferative diabetic retinopathy (NPDR) and the other group with severe/very severe NPDR or proliferative diabetic retinopathy (PDR). The study confirms the influence of HLA genes in the development of DR in Croatian type 1 diabetic patients. In our patients, susceptibility to PDR appears to be primarily associated to DQB1*0201 with the relative risk, RR = 5.29 and DQB1*0302 (RR = 2.84). However, a strong positive correlation between DR and alles DRB1*0301 (RR = 2.12) and DRB1*0402 (RR = 3.01) was also found.

[Hematopoietic stem cell transplantation in treatment of autoimmune diseases]. / Transplantacija krvotvornih maticnih stanica u lijecenju autoimunosnih bolesti.

Hematopoietic stem cell transplantation (HSCT) has become an effective therapeutic option for the treatment of severe cases of autoimmune diseases (AD). Hematopoietic stem cells (HSC) can be collected from the patient (autologous), identical twin (syngenic) or HLA identical donor (allogenous). In allogenous transplantation autoagressive immunological effector cells are substituted with non-autoagressive cells of the donor. Possible graft versus host reaction (GVHD) makes this type of transplantation less attractive. On the other hand, autologous transplantation can induce the >>resetting<< of immunological clock without any fear of GVHD, but it requires previous conditioning. As an alternative option, transplantation ofmesenchymal stem cells (MSS) was developed. MSS has a strong immunosuppressive effect, while it doesn't require previous conditioning, nor does it induce GVHD. Due to the treatment related mortality, these therapeutic option should remain reserved for the most severe cases of AD. Nevertheless, they present a great opportunity for these patients, and even a chance for full recovery.

Alternative donor strategy in unrelated hematopoietic stem cell transplantation - outcome with mismatched donors.

PURPOSE: This study retrospectively investigated the association between the level of human leukocyte antigen (HLA) mismatches (MMs), direction of disparities and differences at particular HLA locus on clinical outcomes of hematopoietic stem cell transplantation (HSCT). Investigated outcomes were overall survival (OS) and disease-free survival (DFS), graft-versus-host disease (GvHD), relapse and non-relapse mortality (NRM). PATIENTS AND METHODS: Study cohort included 108 adult patients transplanted between 2011 and 2021 and their 9/10 mismatched unrelated donors (MMUD). All individuals were typed for HLA-A, -B, -C, -DRB1, -DQB1 and -DPB1 loci using Polymerase Chain Reaction-Sequence Specific Primers, PCR-Sequence Based Typing and Next-Generation Sequencing. All statistical analyses were done in the MedCalc software, version 19.2.6. RESULTS: Patients with MMs at HLA-B locus demonstrated worse OS (P â€‹= â€‹0.0440, HR â€‹= â€‹2.00, n â€‹= â€‹20). Absence of HLA-DRB5 was associated with a higher incidence of GvHD (P â€‹= â€‹0.0112, HR â€‹= â€‹1.93, n â€‹= â€‹67). A lower incidence of GvHD was observed in patients with HLA class II MMs compared to patients with HLA class I MMs (P â€‹= â€‹0.0166, HR â€‹= â€‹1.94, n â€‹= â€‹29). Finally, analysis of PIRCHE score (PS) impact revealed that patients with HLA class II PS â€‹> â€‹10 in GvH direction showed higher incidence of GvHD compared to patients with HLA class II PS â€‹< â€‹10 (P â€‹= â€‹0.0073, HR â€‹= â€‹2.01, n â€‹= â€‹55). CONCLUSION: Obtained results undisputedly indicate the necessity to further investigate this matter on a larger patient group, with focus on specific HLA alleles to define precisely priority criteria for selecting the best donor for all patients, thus improving the outcome of HSCT with an MMUD.

Hantavirus Pulmonary Syndrome Caused by Puumala Orthohantavirus-A Case Report and Literature Review.

In this article, we report on a rare case of acute respiratory distress syndrome (ARDS) caused by the Puumala orthohantavirus (PUUV), which is typically associated with hemorrhagic fever with renal syndrome (HFRS). This is the first documented case of PUUV-associated ARDS in Southeast Europe. The diagnosis was confirmed by serum RT-PCR and serology and corroborated by phylogenetic analysis and chemokine profiling. The patient was a 23-year-old male from Zagreb, Croatia, who had recently traveled throughout Europe. He presented with fever, headache, abdominal pain, and sudden onset of ARDS. Treatment involved high-flow nasal cannula oxygen therapy and glucocorticoids, which resulted in a full recovery. A systematic literature review identified 10 cases of hantavirus pulmonary syndrome (HPS) caused by PUUV in various European countries and Turkey between 2002 and 2023. The median age of patients was 53 years (range 24-73), and six of the patients were male. Most patients were treated in intensive care units, but none received antiviral therapy targeting PUUV. Eight patients survived hospitalization. The presented case highlights the importance of considering HPS in the differential diagnosis of ARDS, even in areas where HFRS is the dominant form of hantavirus infection.

Replication of genetic susceptibility loci for testicular germ cell cancer in the Croatian population.

Genome-wide association studies in patients with testicular germ-cell tumors (TGCT) from Great Britain and the United States have identified six susceptibility loci in or near biologically plausible candidate genes. However, these loci have not been replicated in an independent European sample. We performed a genetic replication study of previously identified TGCT susceptibility loci in a Croatian case-control sample and performed additional analyses as concerning histological subtypes or tumor staging. We analyzed six single-nucleotide polymorphisms [rs2900333 (ATF7IP), rs210138 (BAK1), rs755383 (DMRT1), rs995030 (KITLG), rs4624820 (SPRY4), and rs4635969 (TERT/CLPTM1L)], each representing one of the published susceptibility loci/genes. Five susceptibility loci were found to be also associated in the Croatian population with P-values between 2.1e-10 (rs995030; odds ratio [OR] 3.08) and 0.01739 (rs4635969; OR 1.37), which remained statistically significant after correction for multiple testing. Although rs2900333 near ATF7IP just showed borderline association with all-TGCT (OR 1.24, P = 0.062), it showed significant association with the more aggressive forms of the tumor (OR 1.51, P = 0.0067)-a clinically interesting finding, which however has to be replicated in an independent sample. Assessment of cumulative risks revealed that men with at least seven risk alleles have a more than 2.5-fold increased disease risk (OR = 2.73, 95% confidence interval = 1.98-3.79). In summary, we independently replicated the majority of TGCT susceptibility loci identified previously in a Croatian sample and suggested a possible role of genetic variation near ATF7IP in regulating disease progression.

Diversity of HLA-B*35 alleles and haplotypes among Croatians.

OBJECTIVES: Investigation of HLA-B*35 subtypes and haplotypes among Croatians. METHODS: 4000 randomly selected unrelated donors from Croatian Bone Marrow Donor Registry were typed for HLA-A, -B and -DRB1 by PCR-LabType®SSO method. RESULTS: Four different B*35 alleles (*35:01, *35:02, *35:03, *35:08) were found. Three of them were with similar frequencies as in other European Caucasians, while HLA-B*35:03 was two times more frequent in our population. Predicted haplotypes were also in accordance with present data from other populations. CONCLUSIONS: This study should be of benefit in the unrelated haematopoietic stem cell transplantation (HSCT) program. It should facilitate the recipient-donor matching and the selection of a suitable population for further searches.

The influence of tumor necrosis factor microsatellite polymorphisms on patient survival following hematopoietic stem cell transplantation.

AIM: To investigate the influence of tumor necrosis factor (TNF) microsatellite polymorphisms on patient survival following hematopoietic stem cell transplantation. METHODS: We analyzed TNFa, TNFb, and TNFd microsatellites among 100 patients who underwent allogeneic hematopoietic stem cell transplantation from a human leukocyte antigen (HLA)-identical sibling donor at the Internal Clinic of the University Hospital Center Zagreb in the period 2001-2009. The analysis was performed using polymerase chain reaction amplification and electrophoresis on a polyacrylamide gel in an automated sequencer. RESULTS: There was no significant difference in patient survival with respect to the allele length at a given microsatellite. However, a significantly lower survival rate was noticed among patients who were positive for TNFa8 allele (P<0.001) and a significantly higher survival rate among those who were positive for TNFa10 allele (P=0.0220). CONCLUSION: These results for the first time suggest an influence of TNFa microsatellite on patient survival following HSCT and indicate a need for further studies of this microsatellite.

Various approaches for accessing the influence of human leukocyte antigens disparity in haploidentical stem cell transplantation.

INTRODUCTION: We investigated the association of HLA on clinical outcomes in our cohort of patients in the haplo-HSCT program using the HLAMatchmaker (EM) and PIRCHE score (PS) algorithms. METHODS: The group comprised 64 patients (male = 35-54.7%, female 29-45.3%; median age 43 years) and their related haplo-HSCT donors (male = 30-46.9%, female 34-53.1%). HLA-A/B/C/DRB1/DQB1/DPB1 loci were analyzed. RESULTS: Multivariate analysis of the association between different HLA or patient/donor-related parameters and clinical outcome revealed the following associations with statistical significance: GvHD and HLA class I PS in the GvH direction (p = .0420) and relapse with diagnosis (p = .0163). For OS, the only variable showing a tendency of association was the source of HSCT (p = .0965). CONCLUSION: Combined results of univariate and multivariate analysis suggest that the patients awaiting the selection of the best haplo-HSCT donor could benefit the most from the combination of all three approaches, in cases when a suitable donor can be chosen from a number of potential donors.

Pilot study of the association between the HLA region and testicular carcinoma among Croatian patients.

OBJECTIVES: To analyze the distribution of HLA alleles and HLA microsatellite alleles in Croatian patients with testicular carcinoma, compare it with that of healthy controls and investigate whether the polymorphism within the HLA region could be associated with the development of testicular cancer. METHODS: Genomic DNA was isolated from the peripheral blood of 24 patients with testicular germ cell tumors (TGCT). Patients and controls were typed for HLA class I and class II polymorphism by the PCR-SSO method. Nine HLA microsatellites were analyzed by PCR and electrophoresis in an automated sequencer. RESULTS: No significant deviation in the distribution of frequencies at HLA class I alleles was observed between patients and controls. Among HLA class II alleles, a statistically significant increase in the frequency of the HLA-DPB1*1701 allele was found among patients. The frequency of the HLA-DRB1*07-DQA1*0201-DQB1*0202 haplotype was increased in patients in comparison to the controls. Analysis of HLA microsatellites showed an increased frequency of D6S291-3 allele (p(corr) = 0.0455, OR = 3.05) among patients. CONCLUSIONS: The observed association of the disease and the DPB1*1701 allele as well as with the D6S291-3 allele suggests that this part of the HLA region might be involved in the pathogenesis of TGCT. Our data provide a basis for further studies about the correlation between the HLA region and testicular cancer.

The distribution of HLA alleles among children with atopic asthma in Croatia.

Allergic asthma is a multifactorial disease involving well known environmental factors and less identified genetic components. In several studies the HLA genes have been implicated in the development of asthma and atopy, but the importance of these associations remains unclear. The aim of the present study was to analyse the distribution of specificities at HLA class I loci (-A and -B) and HLA class II locus (-DRB1) in a group of 143 Croatian children with atopic asthma, regarding total serum IgE and specific IgE against common inhalant allergens, as well as their connection with different asthmatic phenotypes and to identify HLA genotype which increases the risk for atopy or asthma or which has a protective effect. As controls we used a group of 163 healthy unrelated individuals. HLA class I antigens were determined by serology, while DRB1 specificities were detected by polymerase-chain reaction amplification and hybridisation with sequence specific oligonucleotide probes method (PCR-SSOP). We found no significant correlation between any of the HLA-A antigens and asthma, atopy or associated atopic phenotypes. At HLA-B locus, HLA-B8 antigen was significantly increased among asthmatic patients (p = 0.002), patients with high total serum IgE (p = 0.002), as well as among patients sensitizated to Dermatophagoides pteronyssinus (Der p) (p = 0.014) and among patients sensitizated to Der p + Dactylis glomerata (Dact g) or Ambrosia elatior (Amb a) (p = 0.004). Among HLA-DRB1 specificities, HLA-DRB1 *01 showed positive correlation with asthma and atopy (p = 0.034), while HLA-DRB1*03 specificity was observed with significantly higher frequency among patients with total serum IgE > or = 400 KU/L (p = 0.048). HLA-DRB1*16 specificity was observed with significantly lower frequency among patients with asthma only in comparison to healthy controls (p = 0.027) and to patients with asthma and allergic rhinitis (p = 0.005). In conclusion, our data suggest that HLA specificities play a relevant role in predisposition to asthma, as well as in different clinical forms of atopic diseases. HLA-B8, HLA-DRB1*01 and HLA-DRB1*03 genotype increases the risk for atopic asthma and high serum IgE.

[The connection between HLA microsatellites and HLA-B*27 gene in patients with psoriatic arthritis in Croatian population]. / Povezanost mikrosatelita HLA i gena HLA-B*27 u bolesnika s psorijaticnim artritisom u hrvatskoj populaciji.

The polymorphism at HLA microsatellites (D6S248, D6S2674, D6S2811 and D6S273) among patients with psoriatic arthritis (PsA) (N = 22) and healthy control subjects (K; N = 94), as well as haplotypic associations between tested loci were analysed in this study. All subjects were previously typed for HLA-A and -B by PCR-SSP method and were HLA-B*27 positive. HLA microsatellites were analysed using PCR-STR method and electrophoresis in an ALFexpress sequencer. The results demonstrated statistically significant P value for following alleles: D6S273-3 (PsA-21.1% vs. K-4.9%; P = 0.0013) and D6S273-4 (PsA-15.8% vs. K-32.1%; P = 0.0180). Analysis of haplotypic associations showed the only statistically significant difference for combination HLA-B*27/D6S273-4 (PsA-10.5% vs. K-40.2%; P = 0.0164). The results presented in this study lead to the assumption that some other gene/s involved in ethiology of PsA are located in the proximity of D6S273 microsatellite, but in order to reach a final conclusion, an increase in the number of patients is necessary.

Mapping the Human Leukocyte Antigen Diversity among Croatian Regions: Implication in Transplantation.

In the present study, HLA allele and haplotype frequencies were studied using the HLA data of 9277 Croatian unrelated individuals, typed using high-resolution methods for the HLA-A, -B, -C, and -DRB1 loci. The total numbers of observed alleles were 47 for HLA-A, 88 for HLA-B, 34 for HLA-C, and 53 for HLA-DRB1. HLA-A∗02:01 (29.5%), B∗51:01 (10.5%), C∗04:01 (15.8%), and DRB1∗16:01 (10.4%) were the most frequent alleles in the Croatian general population. The three most frequent haplotypes were HLA-A∗01:01~C∗07:01~B∗08:01~DRB1∗03:01 (4.7%), HLA-A∗03:01~C∗07:02~B∗07:02~DRB1∗15:01 (1.7%), and HLA-A∗02:01~C∗07:01~B∗18:01~DRB1∗11:04 (1.5%). Allele and haplotype frequencies were compared between national and regional data, and differences were observed, particularly in the North Croatia region. The data has potential use in refining donor recruitment strategies for national registries of volunteer hematopoietic stem cell donors, solid organ allocation schemes, and the design of future disease and anthropological studies.

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.

The Role of HLA and KIR Immunogenetics in BK Virus Infection after Kidney Transplantation.

BK virus (BKV) is a polyomavirus with high seroprevalence in the general population with an unremarkable clinical presentation in healthy people, but a potential for causing serious complications in immunosuppressed transplanted patients. Reactivation or primary infection in kidney allograft recipients may lead to allograft dysfunction and subsequent loss. Currently, there is no widely accepted specific treatment for BKV infection and reduction of immunosuppressive therapy is the mainstay therapy. Given this and the sequential appearance of viruria-viremia-nephropathy, screening and early detection are of utmost importance. There are numerous risk factors associated with BKV infection including genetic factors, among them human leukocyte antigens (HLA) and killer cell immunoglobulin-like receptors (KIR) alleles have been shown to be the strongest so far. Identification of patients at risk for BKV infection would be useful in prevention or early action to reduce morbidity and progression to frank nephropathy. Assessment of risk involving HLA ligands and KIR genotyping of recipients in the pre-transplant or early post-transplant period might be useful in clinical practice. This review summarizes current knowledge of the association between HLA, KIR and BKV infection and potential future directions of research, which might lead to optimal utilization of these genetic markers.

Detection of novel and confirmation of very rare and rare HLA alleles by next generation sequencing in Croatia.

Routine HLA typing in clinical practice encompassing solid organ and hematopoietic stem cells transplantation programs, disease association typing, volunteer marrow donor typing and population studies, provided a large dataset for studying HLA allele polymorphism in the Croatian population which led to the identification of new, very rare and rare HLA alleles. Over the last 4 years we have identified six new HLA alleles (HLA-A*01:200, A*02:836, A*11:01:01:44, B*08:251, B*18:169 and C*05:46:01:02) and a number of very rare (HLA-B*08:78, DRB1*12:39, DRB1*13:23:02 and DQB1*06:09:04) or rare (HLA-A*24:41, B*39:40:01N, B*51:78:01, DRB1*01:31 and DRB1*14:111) alleles using sequence-based typing methods. The reported data enhance the knowledge about HLA polymorphisms in the Croatian population and provide a foundation for further studies in population genetics.