HLA-G, LILRB1 and LILRB2 Variants in Zika Virus Transmission from Mother to Child in a Population from South and Southeast of Brazil.

During the 2015-2016 epidemic, Brazil was the country with the highest rate of Zika virus (ZIKV) infection in the Americas. Twenty-nine percent of pregnant women positive for ZIKV exhibited ultrasound scans with fetus anomalies. Human leukocyte antigen-G (HLA-G) exerts immunoregulatory effects by binding to inhibitory receptors, namely LILRB1 and LILRB2, thus preventing mother-fetus rejection and vertical pathogen transmission. The binding of HLA-G to one of its receptors modulates both innate and adaptive immunity. However, in a viral infection, these molecules may behave as pathogenic mediators shifting the pregnancy environment from an anti-inflammatory profile to a pro-inflammatory phenotype. Genetic mutations might be associated with the change in phenotype. This study aimed to explore the possible role of polymorphic sites in HLA-G, LILRB1 and LILRB2 in mother-fetus ZIKV transmission. Polymorphisms were detected by direct sequencing. Differences in allele and/or genotype frequencies for each SNP analyzed among ZIKV non-transmitting and transmitting mother-child pairs, among ZIKV-transmitting and non-transmitting mothers and between ZIKV-infected and non-infected children were compared by Mid-P exact test or Yates' correction. Significant susceptibility of ZIKV vertical transmission is suggested in ZIKV-transmitting and non-transmitting mothers and ZIKV-infected and non-infected children for LILRB1_rs1061684 T/T (p = 0.03, Pc = 0.06, OR = 12.4; p = 0.008, Pc = 0.016, OR = 16.4) and LILRB1_rs16985478 A/A (p = 0.01, Pc = 0.02, OR = 19.2; p = 0.008, Pc = 0.016, OR = 16.4). HLA-G_rs1710 (p = 0.04, Pc = 0.52, OR = 4.30) was also a susceptibility factor. LILRB2_rs386056 G/A (p = 0.02, Pc = 0.08, OR = 0.07), LILRB2_rs7247451 G/G (p = 0.01, Pc = 0.04, OR = 0.04) and HLAG_rs9380142 T/T (p = 0.04, Pc = 0.52, OR = 0.14) were suggested as protective factors against vertical transmission. The current study suggests that polymorphic sites in the LILRB1 and HLA-G genes might be associated with mother-to-child ZIKV transmission while LILRB2 might be associated with protection against ZIKV transmission in the womb in a population from the south and southeast of Brazil.

Lack of association of the KIR and HLA class I ligands with ZIKV infection in south and southeast of Brazil.

BACKGROUND: Zika virus (ZIKV) is an emerging arbovirus associated with foetal malformations and neurological complications. The infection is usually associated with mild symptoms. The comparison between the allelic frequency of polymorphic genes in symptomatic infected individuals in the population can clarify the pathogenic mechanisms of ZIKV. During ZIKV infection, cytokines are produced and natural killer (NK) cells are recruited, whose activation depends on signaling pathways activated by specific receptors, such as killer cell immunoglobulin-like receptors (KIR). These molecules interact with human leukocyte antigen (HLA) class I ligands and are encoded by polymorphic genes. OBJECTIVES: This study aimed to evaluate the frequency of allelic variants of the genes encoding the KIR receptors and their HLA class I ligands in 139 symptomatic ZIKV-patients and 170 controls negative for the virus, and to evaluate the role of these variants for ZIKV susceptibility. METHODS: KIR and HLA class I genes were genotyped using the polymerase chain reaction-sequence specific oligonucleotide (PCR-SSO) technique. FINDINGS: No significant differences in the frequency distribution of KIRs and KIR-HLA in patients compared to controls were observed. MAIN CONCLUSIONS: KIR and its HLA ligands might play a minor role in ZIKV infection in the south and southeast Brazilian individuals.

Toll-like receptor gene polymorphisms in patients with myeloproliferative neoplasms.

Toll-like receptors (TLRs) are a family of transmembrane receptors whose signaling control cellular processes of cell proliferation, survival, apoptosis, angiogenesis, remodeling, and repair of tissues. Polymorphisms in TLR genes can change the balance between pro and anti-inflammatory cytokines, modulating the risk of infection, chronic inflammation, and cancer. Although many studies have demonstrated the direct involvement of TLR signaling in the benefit of tumor cells in certain cancers, little is known about the influence of these gene polymorphisms on myeloproliferative neoplasms (MPNs). In this context, the objective of the study was to investigate a possible association between the TLR polymorphisms and the development of MPNs. 167 patients diagnosed with MPN and 222 healthy controls from the same region were evaluated. Genomic DNA was extracted and the TLR2 (rs5743708), TLR4 (rs4986790, rs4986791), TLR9 (rs5743836, rs187084) and JAK2V617F polymorphisms were genotyped by PCR-RFLP. The statistical analysis was performed by OpenEpi and SNPstat software. The JAK2V617F mutation was found in 68.32% of patients. TLR9-1486C/T CT genotype was less frequent in patients with polycythemia vera (PV) (OR 0.39, 95% CI 0.20-0.78, P = 0.025). When haplotype frequencies were analyzed, -1237T/-1486C (TLR9) was also less frequent in men (OR 0.58, 95% CI 0.36-0.94) and JAK negative men patients (OR 0.43, 95% CI 0.21-0.88). We can infer that the TLR9-1486 CT genotype could be associated with protection for PV and the TLR9-1237T/-1486C haplotype, protection for men, as well as for JAK negative men patients with MPN. There were no associations between TLR2 and TLR4 gene polymorphisms and MPN.

Association of MICA and HLA-B alleles with leprosy in two endemic populations in Brazil.

Leprosy is a prevalent disease in Brazil, which ranks as the country with the second highest number of cases in the world. The disease manifests in a spectrum of forms, and genetic differences in the host can help to elucidate the immunopathogenesis. For a better understanding of MICA association with leprosy, we performed a case-control and a family-based study in two endemic populations in Brazil. MICA and HLA-B alleles were evaluated in 409 leprosy patients and in 419 healthy contacts by PCR-SSOP-Luminex-based technology. In the familial study, analysis of 46 families was completed by direct sequencing of all exons and 3'/5'untranslated regions, using the Ilumina MiSeq platform. All data were collected between 2006 and 2009. Statistical analysis was performed using the Chi-square or Fisher's exact test together with a multivariate analysis. Family-based association was assessed by transmission disequilibrium test (TDT) software FBAT 2.0.4. We found associations between the haplotype MICA*002-HLA-B*35 with leprosy in both the per se and the multibacillary (MB) forms when compared to healthy contacts. The MICA allele *008 was associated with the clinical forms of paucibacillary (PB). Additionally, MICA*029 was associated with the clinical forms of MB. The association of MICA*029 allele (MICA-A4 variant) with the susceptibility to the MB form suggests this variant for the transmembrane domain of the MICA molecule may be a risk factor for leprosy. Two MICA and nine HLA-B variants were found associated with leprosy per se in the Colônia do Prata population. Linkage disequilibrium analysis revealed perfect linkage disequilibrium (LD) between HLA-B markers rs2596498 and rs2507992, and high LD (R2  = .92) between these and the marker rs2442718. This familial study demonstrates that MICA association signals are not independent from those observed for HLA-B. Our findings contribute the knowledge pool of the immunogenetics of Hansen's disease and reveals a new association of the MICA*029 allele.

COVID-19: The question of genetic diversity and therapeutic intervention approaches.

Coronavirus disease 2019 (COVID-19), caused by the Severe Acute Respiratory Syndrome Coronavirus type 2 (SARS-CoV-2), is the largest pandemic in modern history with very high infection rates and considerable mortality. The disease, which emerged in China's Wuhan province, had its first reported case on December 29, 2019, and spread rapidly worldwide. On March 11, 2020, the World Health Organization (WHO) declared the COVID-19 outbreak a pandemic and global health emergency. Since the outbreak, efforts to develop COVID-19 vaccines, engineer new drugs, and evaluate existing ones for drug repurposing have been intensively undertaken to find ways to control this pandemic. COVID-19 therapeutic strategies aim to impair molecular pathways involved in the virus entrance and replication or interfere in the patients' overreaction and immunopathology. Moreover, nanotechnology could be an approach to boost the activity of new drugs. Several COVID-19 vaccine candidates have received emergency-use or full authorization in one or more countries, and others are being developed and tested. This review assesses the different strategies currently proposed to control COVID-19 and the issues or limitations imposed on some approaches by the human and viral genetic variability.

IL8 and IL17A polymorphisms associated with multibacillary leprosy and reaction type 1 in a mixed population from southern Brazil.

We evaluated the influence of the IL8 T-738A (nonidentified rs), IL8 T-353A (rs4073), IL17A G197A (rs2275913), and IL17F T7488C (rs763780) single-nucleotide polymorphisms on leprosy. The AA genotype of IL8 T-353A was observed as a risk factor for multibacillary leprosy, regardless of gender and age-of-onset of disease, considering the recessive model (OR, 3.8; 95% CI, 1.1-13.5; P, 0.023). Furthermore, the AA genotype of IL17A G197A was associated with leprosy type 1 reaction (OR, 2.4; 95% CI, 1.1-5.1; P, 0.026) when compared to the group without reaction, which was adjusted for gender and age-of-onset of disease by the model log additive. These results indicate association of IL8 and IL17A polymorphisms with the progression to multibacillary leprosy and with the type 1 reaction, respectively.

The Influence of TLR4, CD14, OPG, and RANKL Polymorphisms in Periodontitis: A Case-Control Study.

The pathogenesis of periodontitis involves a complex interaction between the microbial challenge and the host immune response. The individual immunoinflammatory response has a great contribution in the pathogenesis of the disease and becomes a trigger in the process of bone remodeling which is a characteristic of the disease. Thus, the aim of this study was to evaluate the influence of the TLR4 A896G (rs4986790), TLR4 C1196T (rs4986791), CD14 C-260T (rs2569190), RANKL (TNFSF11, rs2277438), and OPG (TNFSF11B C163T, rs3102735) polymorphisms in periodontitis. A case-control study was conducted on patients with periodontitis (N = 203) and controls (N = 213) over 30 years of age, without diabetes mellitus, acute infections, and osteoarthritis, and patients without aggressive periodontitis, i.e., stage IV and C degree of periodontitis, and any periodontal treatment performed in the last 6 months. Genotypes were determined by the PCR-RFLP and sequencing method. The frequency comparisons between case and controls were performed using the chi-square test and logistic regression (OpenEpi and SNPStats software). The risk (OR) was evaluated for values of P < 0.05. Differences in TLR4, CD14, RANKL, and OPG genotype and allele frequency distributions were not observed between patients and controls. However, some variants were a risk factor for the development of periodontitis when considering gender and smoking habits. The TLR4 896 A/G genotype was a risk factor for periodontitis in males (OR = 2.86), and the TLR4 1196C/C genotype was a risk factor for nonsmoking males (OR = 1.85) when compared to women. The RANKL A/A and the OPG T/C genotype was associated with the risk of the disease in nonsmoking men compared to nonsmoking women with the same genotype (OR = 1.96 and OR = 2.9, respectively). In conclusion, TLR4, CD14, RANKL, and OPG variants were not associated with periodontitis. However, TLR4, RANKL, and OPG polymorphisms could be a risk for periodontitis in males regardless of smoking habits.

IL18 Polymorphism and Periodontitis Susceptibility, Regardless of IL12B, MMP9, and Smoking Habits.

Genetic variations contribute to the susceptibility in the development of periodontitis. The aim of this study was to investigate the influence of IL18, IL12, and MMP9 polymorphisms in the chronic periodontitis. This case-control study involved 381 individuals matched by gender and age. Genotyping of IL18 (rs187238 and rs1946518) and IL12B (rs3212227) was performed by PCR-SSP and PCR-RFLP was used for MMP9 (rs3918242). IL-18 and MMP-9 were quantified in the serum by ELISA. SNPStats and OpenEpi software were used for statistical analysis and, in order to eliminate smoking as a confounding factor, the analyses were also performed in nonsmoking subjects. The IL18-137G/C genotype was associated with the risk of chronic periodontitis in nonsmokers (P c = 0.03; OR = 1.99; overdominant inherence model). In the multivariate analyses, homozygous IL18-137G/G and IL18-607C/C were more frequent in males compared to women with these same genotypes (OR = 2.51 and OR = 3.30, respectively). The serum levels of the IL-18 in patients were higher than those in healthy controls (P = 0.005). IL12B and MMP9 polymorphisms and MMP-9 serum concentration were similar in patients and controls. In this study, IL18 was associated with chronic periodontitis susceptibility. Men had greater risk than women for developing the disease when IL18 polymorphism was considered and the susceptibility was independent of the smoking status.

The distribution of HLA haplotypes in the ethnic groups that make up the Brazilian Bone Marrow Volunteer Donor Registry (REDOME).

The Registries of Bone Marrow Donors around the world include more than 30 million volunteer donors from 57 different countries, and were responsible for over 17,000 hematopoietic stem cell transplants in 2016. The Brazilian Bone Marrow Volunteer Donor Registry (REDOME) was established in 1993 and is the third largest registry in the world with more than 4.3 million donors. We characterized HLA allele and haplotypes frequencies from REDOME comparing them with the donor self-reported race group classification. Five-locus haplotype frequencies (A~C~B~DRB1~DQB1) were estimated for each of the six race groups, resolving phase and allelic ambiguity using the expectation-maximization (EM) algorithm. The top 100 haplotypes in the race groups were separated into eight clusters of haplotypes, based on haplotype similarity, using CLUTO. We present HLA allele and haplotype frequency data from six race groups from 2,938,259 individuals from REDOME. The most frequent haplotype was the same for all groups: A*01:01g~C*07:01g~B*08:01g~DRB1*03:01g~DQB1*02:01g. Some frequent haplotypes such as A*02:01g~C*16:01g~B*44:03~DRB1*07:01g~DQB1*02:01g was not found in people with Preta (Sub-Saharan African descent). A cluster including Branca (European) and Parda or non-informed (admixed) could be distinguished from both Preta (SubSaharan) and Indígena (Amerindian) groups, and from the Amarela (Asian) ones, which clustered with their original population. These results have implications on cross-population matching and can help in donor searches and population-based recruitment strategies.

Red blood cell alloimmunization in patients with sickle cell disease: correlation with HLA and cytokine gene polymorphisms.

BACKGROUND: The reason for the difference in susceptibility to red blood cell (RBC) alloimmunization among patients with sickle cell disease (SCD) is not clearly understood and is probably the result of multiple factors. Our hypothesis is that genetic polymorphisms are associated with RBC alloimmunization. STUDY DESIGN AND METHODS: We investigated the possible association of susceptibility to RBC alloimmunization with polymorphisms of HLA and cytokines genes in 161 SCD patients prior exposed to RBC transfusion. Cytokine gene polymorphisms were analyzed by polymerase chain reaction (PCR) and TaqMan assays. HLA Class I genotyping was performed using PCR-specific sequence of oligonucleotides. Polymorphism frequencies were compared using the Fisher's exact test. RESULTS: Our results revealed increased percentage of the A allele and the GA genotype of the TNFA -308G/A cytokine among alloimmunized patients when compared to nonalloimmunized patients (A allele, 16.4% vs. 6.8%, p = 0.004; GA genotype, 32.8% vs. 11.7%, p = 0.0021). In addition, the IL1B -511T allele and the IL1B -511TT and CT genotype frequencies were overrepresented among alloimmunized patients (T allele, 53.0% vs. 37.5%, p = 0.0085; CT + TT genotypes, 81.82% vs. 60.87%, p = 0.0071). In relation to HLA Class I, we found a higher frequency of HLA-DRB1*15 among patients alloimmunized to Rh antigens when compared to nonalloimmunized patients (15.63% vs. 6.98%, p = 0.044). CONCLUSION: Brazilian SCD patients with the TNFA, IL1B, and HLA-DRB1 gene polymorphisms were at increased risk of becoming alloimmunized by RBC transfusions. These findings may contribute to the development of future therapeutic strategies for patients with SCD with higher susceptibility of alloimmunization.

Genetic polymorphisms of human platelet antigens in Euro-African and Japanese descendants from Parana, Southern Brazil.

The frequency distributions of HPA-1 to HPA-6 and HPA-15 were evaluated in two Brazilian populations from Parana: a mixed population of predominantly Caucasians and a population of Japanese descendants. Genotyping was performed by PCR-SSP in 364 unrelated individuals. Differences in the distribution of HPA highlight diversity in Brazilian miscegenation and the importance of formation of the HPA panel composed of regional blood donors.

Association of TNF polymorphisms with JAK2 (V617F) myeloproliferative neoplasms in Brazilian patients.

The classical chromosome Philadelphia-negative myeloproliferative neoplasms (MPNs) are a group of disorders that share clinical, hematological, and histological features. Proinflammatory cytokines such as tumor necrosis factor-α (TNF-α) are elevated in patients with MPN. The aim of this study was to verify the association between the polymorphisms of TNF gene (-308G/A and -238 G/A) in BCR-ABL-negative MPN in our population. Blood samples obtained from MPN patients were genotyped for the JAK2V617F mutation and both TNF polymorphisms using PCR-RFLP. Thirty three (26.8%) patients with polycythemia vera (PV), 35 (28.7%) essential thrombocythemia (ET), 22 (17.7%) primary myelofibrosis (PMF), and 33 (26.8%) with unclassifiable MPN (MPNu) were included in the study. The JAK2 V617F mutation was detected in 94 (76.42%) patients. Were observed a significant increase on the frequency of the TNF-238 GA genotype in MPN patients compared to controls (OR=2.21, 95% CI=1.02-4.80, P<0.04). The distribution of the genotypes and allelic frequencies of TNF-308 was significantly different among the MPNs, JAK2V617F positive, PV and PMF, and controls. Our data has demonstrated that the polymorphisms on TNF-238 GA, TNF-308 GA were associated to MPN development in this population, triggered by JAK2 V617F mutation.

Profile of Rh, Kell, Duffy, Kidd, and Diego blood group systems among blood donors in the Southwest region of the Paraná state, Southern Brazil.

The aim of this study was to assess the distribution of alleles and genotypes of the blood group systems Rh, Kell, Duffy, Kidd, and Diego in 251 regular blood donors registered in the hemotherapy unit of the Southwestern region of Paraná, Southern Brazil. The frequencies were obtained by direct counting on a spreadsheet program and statistical analyses were conducted in order to compare them with other Brazilian populations using chi-squared with Yates correction on OpenEpi software. The frequencies of RHD* negative, RHCE*c/c and RHCE*e/e were higher than expected for the Caucasian population. A difference was also observed for FY alleles, FY*01/FY*01 genotype and FY*02N.01 -67T/C (GATA Box mutation). Two homozygous individuals were defined as a low frequency phenotype K + k- (KEL*01.01/KEL*01.01) and, for Diego blood group system the rare DI*01 allele was found in ten blood donors, of which one was DI*01/DI* 01 (0.4%). The allele and genotype frequencies of Kidd blood group system were similar to expected to Caucasians. The results showed the direction in which to choose donors, the importance of extended genotyping in adequate blood screening and the existence of rare genotypes in Brazilian regular blood donors.

Frequency of RHD variants in Brazilian blood donors from Parana State, Southern Brazil.

The Rh blood group system is one of the most complex, polymorphic and immunogenic blood group systems in humans. Some individuals produce a weak or a partial D as a result of RHD and RHCE gene conversion events and RHD point mutations. Because the incidence of RHD variants differs considerably among ethnic groups, the objective of this study was to establish the frequency of blood donors carrying some weak and partial RHD, at the molecular level, in 400 blood donors from the North/Northwest of the state of Parana, Southern Brazil. Another 30 blood donors whose RhD typing results in serology were inconclusive were also included. In this mixed Brazilian population, the most frequent weak D types were 1, 4, 3 and 2 (frequencies of 4.35%, 2.32%, 1.46% and 0.29%, respectively; total of 8.41%) and partial D was found in 2.90% of samples carrying the RHD gene. For samples with inconclusive RhD typing, 53.33% of them presented weak and partial RHD, and 43.75% had concomitantly more than one RHD variant. Our results demonstrate the presence of Caucasian and African D variants. This knowledge can contribute to the safety of transfusion strategies in this ethnic admixture population.

Genetics factors associated with myelodysplastic syndromes.

The myelodysplastic syndromes (MDS) are a clinically and cytogenetically heterogeneous group of clonal diseases. Clonal chromosomal abnormalities are observed in 30-50% of patients with MDS. The deletions are among the most common alterations, and often involve the long arms of chromosomes 5, 7, 8, 13, and 20 and the short arms of chromosomes 12 and 17. The advent of new technologies for the detection of genetic abnormalities led to the description of a new set of recurrent mutations, leading to new insights into the pathophysiology of MDS. The recent recognition that genes involved in the regulation of histone function (EZH2, ASXL1, and UTX) and DNA methylation (DNMT3A, IDH1/IDH2, and TET2) are frequently mutated in MDS, has led to the proposal that there is an important link between genetic and epigenetic alterations in this disease. In fact, regulatory factors have also been considered as miR-143/miR-145, miR-146a, miR-125a and MiR-21. Somatic mutations may influence the clinical phenotype but are not included in current prognostic scoring systems. In recent years research has brought new insights into these diseases, but few of the findings are sufficiently robust to be incorporated into the clinical routine at this time. Thus, the aim of this study was to review the role of genetic factors involved in the diagnosis and development of the different phenotypes of MDS.

The Influence of Interleukin 17A and IL17F Polymorphisms on Chronic Periodontitis Disease in Brazilian Patients.

A case-control study was conducted on patients with chronic periodontitis (CP) and healthy controls with the aim of evaluating possible association between interleukin 17A (IL17A) G197A (rs2275913) and IL17F T7488C (rs763780) polymorphisms and periodontitis. Genotypes were determined by PCR-RFLP method. Statistical analyses were conducted using the OpenEpi and SNPStas software to calculate Chi-square with Yates correction or Fisher's exact tests, odds ratios (OR), and 95% confidence intervals (CIs). SNPStas software was used to calculate Hardy-Weinberg equilibrium. IL17A AA genotype was more frequent in patients with chronic periodontitis (CP) in the codominant and recessive models (P = 0.09; OR = 2.53 and P = 0.03; OR = 2.46, resp.), the females with CP (P = 0.01, OR = 4.34), Caucasoid patients with CP (P = 0.01, OR = 3.45), and nonsmoking Caucasian patients with CP (P = 0.04, OR = 3.51). The IL17A A allele was also more frequent in Caucasians with CP (P = 0.04, OR = 1.59). IL17F T7488C polymorphism was not associated with chronic periodontitis. In these patients from Southern Brazil, the IL17A rs2275913 polymorphisms, IL17A AA genotype, and the A allele were associated with a susceptibility to chronic periodontitis.

HLA Haplotypes and Genotypes Frequencies in Brazilian Chronic Periodontitis Patients.

Human leukocyte antigens (HLA) have a pivotal role in immune response and may be involved in antigen recognition of periodontal pathogens. However, the associations of HLA with chronic periodontitis (CP) have not been previously studied in the Brazilian population. In an attempt to clarify the issue of genetic predisposition to CP, we examined the distribution of HLA alleles, genotypes, and haplotypes in patients from Southern Brazil. One hundred and eight CP patients and 151 healthy and unrelated controls with age-, gender-, and ethnicity-matched were HLA investigated by polymerase chain reaction with sequence specific oligonucleotides. To exclude smoking as a predisposing factor, statistical analyses were performed in the total sample and in nonsmoking individuals. The significant results showed a positive association of the A∗ 02/HLA-B∗ 40 haplotype with CP (total samples: 4.2% versus 0%, Pc = 0.03; nonsmokers: 4.3% versus 0%, Pc = 0.23) and a lower frequency of HLA-B∗ 15/HLA-DRB1∗ 11 haplotype in CP compared to controls (total samples: 0.0% versus 4.3%, Pc = 0.04; nonsmokers: 0 versus 5.1%, P = 1.0). In conclusion, the HLA-A∗ 02/B∗ 40 haplotype may contribute to the development of CP, while HLA-B∗ 15/DRB1∗ 11 haplotype might indicate resistance to disease among Brazilians.

Influence of KIR genes and their HLA ligands in the pathogenesis of leprosy in a hyperendemic population of Rondonópolis, Southern Brazil.

BACKGROUND: The objective of this study was to investigate the association between KIR genes and the immunopathogenesis of leprosy. METHODS: The types of KIR and HLA genes were evaluated by PCR-SSOP-Luminex in 408 patients with leprosy and 413 healthy individuals. Statistical analysis was performed using the Chi-square or Fisher's exact test and stepwise multivariate analysis. RESULTS: There was a higher frequency of activating KIR genes (KIR2DS1, 2DS2 and 3DS1) together with their HLA ligands in the tuberculoid (TT) group as compared to the lepromatous leprosy (LL) group. KIR2DL2/2DL2-C1 was more frequent in the patient, TT and LL groups than in the control group. Borderline patients presented a higher frequency of inhibitory pairs when compared to the control group, and a higher frequency of activating pairs as compared to the LL group. Multivariate analysis confirmed the associations and demonstrated that being a female is a protective factor against the development of the disease per se and the more severe clinical form. CONCLUSIONS: This study showed that activating and inhibitory KIR genes may influence the development of leprosy - in particular, activating genes may protect against the more aggressive form of the disease - thereby demonstrating the role of NK cells in the immunopathology of the disease.

Rh, Kell, Duffy, Kidd and Diego blood group system polymorphism in Brazilian Japanese descendants.

Polymorphisms of Rh, Kell, Duffy, Kidd and Diego blood group systems were studied in 209 unrelated Brazilian Japanese descendants from South of Brazil. The methods used were multiplex-PCR, AS-PCR and RFLP-PCR. The differences in frequencies among the populations were evaluated using chi-square test. The frequencies for Rh, Kell, Kidd and Diego system were similar to those of the Japanese. RHCE(*)CC, RHCE(*)EE genotypes and FY(*)01 allele were lower and FY(*)01N.01 was higher than Japanese. These differences in the frequencies between Brazilian Japanese descendants and Japanese could indicate a gene flow in Brazilian population and reinforce the importance of this knowledge to achieve safe red blood cells.

Investigation of deletion of 22pb in KIR2DS4 gene in a population of southern Brazil.

BACKGROUND: The aim of this study was to investigate the distribution of full-length and deleted variants of KIR2DS4 in a population of southern Brazil and compare the results with other populations, as well as comparing two techniques, PCR-SSP and PCR-SSO, for typing of variants. METHODS: 258 individuals from southern Brazil were analysed by PCR-SSO ("polymerase chain reaction-sequence specific oligonucleotides", One Lambda, Inc., Canoga Park, CA), of which 161 were also analysed by PCR-SSP. RESULTS: The study population showed similarities with other Caucasian populations; 46.5% of individuals had only KIR2DS4 variants, 21.3% had the full-length form and 25.1% had both forms. CONCLUSION: The frequencies found in both groups (genotyped by PCR-SSP and PCR-SSO) were 100% concordant.