Made available in DSpace on 2016-08-10T10:39:10Z (GMT). No. of bitstreams: 1 THYAGO PEDROSA MAGALHAES.pdf: 2261259 bytes, checksum: 42a1ba331ec79afdea4d0071a56fca2c (MD5) Previous issue date: 2015-03-10 / Multiple sclerosis is a chronic inflammatory disease of the central nervous system, characterized by demyelination and neuronal degeneration, a major cause of disability in young. Subjects an autoimmune response against neuronal auto antigen, with destruction of the myelin sheath, is observed in individuals with genetic predisposition exposed to certain environmental factors. Among the genetic factors, studies suggest a complex interaction between the alleles of the human leukocyte antigen (HLA-DRB1*1501 and DQB1*0602) and the risk of developing the disease. The allele DRB1 * 1501 was associated with the disease in Caucasian patients in North America and Northern Europe, and the DQB1*0602 allele in Caucasians of Northern Europe and African descendant. The aim of this study was to conduct a systematic review and a meta-analysis of studies that investigated the contribution of DRB1*1501 and DQB1*0602 in the risk of developing MS in different populations of the world. A systematic review and meta-analysis were performed on the main publications in the electronic database of PubMed, by using the terms "HLA" "MULTIPLE SCLEROSIS", "DR" "DQ" and "HLA" "MULTIPLE SCLEROSIS" and "BRAZIL "resulting in a total of 181 articles. After reading the articles, 18 met the inclusion criteria and were selected for review. Based on the results it was possible to conclude that the two alleles are more common in MS patients than in controls, with the allele DRB1*1501 more frequent in European and Caucasian populations and the DQB1 * 0602 with a distribution more heterogeneous in populations. The results obtained by the meta-analysis showed a statistically significant association between DRB1 * 1501 and DQB1 * 0602 allele and the risk of developing multiple sclerosis (OR combined DRB1 * 1501 = 2.934, 95% CI: 2.154 to 3.998, p <0, 0001 and DQB1 * 0602 combined OR = 2.906, 95% CI: 2.167 to 3.896, p <0.0001). / A Esclerose Múltipla é uma doença inflamatória crônica do sistema nervoso central, caracterizada por desmielinização e degeneração neuronal, sendo uma importante causa de incapacidade em jovens. Decorre de uma resposta autoimune contra autoantígenos neuronais, com destruição da bainha de mielina em indivíduos com predisposição genética, expostos a determinados fatores ambientais. Dentre os fatores genéticos, estudos apontam para uma interação complexa de alelos do Antígeno Leucocitário Humano (HLA-DRB1*1501 e DQB1*0602), e o risco de desenvolver a doença. O alelo DRB1*1501 foi associado à doença em pacientes caucasianos na América do Norte e Norte da Europa e o alelo DQB1*0602 em caucasianos da Norte da Europa e afrodescentes. O objetivo do estudo foi realizar uma revisão sistemática e meta-análise sobre os estudos que investigaram a contribuição dos alelos DRB1*1501 e DQB1*0602 no risco de desenvolver EM nas diversas populações do mundo. Uma revisão sistemática e uma meta-análise foram realizadas acerca das principais publicações encontradas na base de dados eletrônicas do PUBMED utilizando os termos HLA MULTIPLE SCLEROSIS , DR DQ e HLA MULTIPLE SCLEROSIS e BRAZIL , resultando em um total de 181 artigos. Após a leitura dos artigos, 18 preencheram os critérios de inclusão e foram selecionados para a revisão. Com base nos resultados obtidos dos artigos foi possível concluir que os dois alelos avaliados são mais frequentes em pacientes com Esclerose Múltipla do que em controles, sendo o alelo DRB1*1501 mais comum nas populações europeias e caucasianas e o alelo DQB1*0602 com uma distribuição mais heterogênea nas populações. Os resultados obtidos pela meta-análise demonstraram associações estatisticamente significativas entre os alelos DRB1*1501 e DQB1*0602 e o risco de desenvolver Esclerose Múltipla, (OR combinada DRB1*1501= 2,934, 95% IC: 2,154 3,998, p < 0,0001 e OR combinada DQB1*0602 = 2,906, 95% IC: 2,167 3,896, p < 0,0001).

Os alelos HLA-DRB1, que codificam uma sequência de aminoácidos (QKRAA/QRRAA/RRRAA) nas posições 70 a 74 da terceira região hipervariável da cadeia &#61538;1 do gene DRB1, denominada epítopo compartilhado (EC), estão associados com maior susceptibilidade e gravidade para artrite reumatóide (AR) em diversas populações. Uma nova classificação proposta por Du Montcel et al tem sido desenvolvida para apurar a associação entre HLA-DRB1 e AR. Este estudo foi desenhado com o objetivo de determinar a frequência dos alelos HLA-DRB1 em pacientes brasileiros com AR, e sua associação com o fator reumatoide (FR), anticorpos antipeptídeos citrulinados (ACPA) e lesão radiográfica articular e óssea. Quatrocentos e doze pacientes com AR e 215 controles foram incluídos. A tipificação HLA-DRB1 foi realizada pela reação em cadeia de polimerase (PCR) usando primers específicos e hibridação com oligonucleotídeos de sequência específica (SSOP). A pesquisa de ACPA foi determinada pela técnica de ELISA e a do FR por nefelometria, a avaliação radiográfica realizada pelo método do índice de Sharp modificado de Van Der Heijde. Para análises estatísticas foram utilizados os testes do qui-quadrado, t de Student e a regressão logística. Nos pacientes com AR alelos HLA-DRB1*04:01, *04:04, *04:05 se associaram com AR (p<0,05), embora o amplo intervalo de confiança, vale a pena ressaltar a associação observada com o alelo DRB1*09:01 e a doença (p<0,05). Alelos HLA-DRB1 EC+ foram observados em 62,8% dos pacientes e em 31,1% do grupo controle (OR 3,62; p <0,001) e estiveram associados com ACPA (OR 2,03; p<0,001). Alelos DRB1 DERAA mostraram efeito protetor para a AR (OR 0,42; p<0,001). A análise da nova classificação de HLA-DRB1 mostra que S2 e S3P se associaram a AR (p<0,05). Alelos S2 e/ou S3P esteve presente em 65% dos pacientes e 32% do grupo controle (OR 3,86; p<0,001) e estiveram associados a ACPA (OR.2,11; p=0,001). Alelos S3D, S1, X mostraram efeito protetor para a AR. Os resultados obtidos neste estudo demonstram que pacientes brasileiros com AR de etnia majoritariamente mestiça, alelos HLA-DRB1 avaliados segundo a hipótese do EC e a classificação proposta por Du Montcel estiveram associados à suscetibilidade à doença e à presença de ACPA. / HLA-DRB1 alleles that encode an amino acid sequence at positions 70-74 of the third hypervariable region of the B chain of the DRB1 gene, called shared epitope (SE), are associated with increased susceptibility and severity to rheumatoid arthritis (RA) in different populations. A new classification proposed by Du Montcel et al has been developed to determine the association between HLA-DRB1 and RA. This study was designer to determine the frequency of HLA-DRB1 alleles in Brazilian patients with RA, and its association with rheumatoid factor (RF), citrullinated peptide antibodies (ACPA) and radiographic joint damage and bone. Four hundred and twelve patients with RA and 215 controls were included. The HLA-DRB1 typing was performed by polymerase chain reaction (PCR) using specific primers and hybridization with sequence specific oligonucleotides (SSOP). The survey of ACPA was determined by ELISA and the RF by nephelometry, the radiographic evaluation by index method modified Sharp Van Der Heijde. For statistical analysis we used the chi-square, Student and logistic regression. In patients with rheumatoid arthritis HLA-DRB1*04:01, *04:04, *04:05 are associated with RA (p<0,05), although the wide confidence interval, it is worth noting the association observed with the DRB1*09:01 allele and the disease (p<0,05). HLA-DRB1 SE+ were observed in 62.8% of patients and in 31.1% of the control group (OR 3.62, p<0,001) and were associated with ACPA (OR 2.03, p<0,001). DERRA alleles showed a protective effect against RA (OR 0,42, p<0,001). The analysis of the new classification of HLA-DRB1 shows that S2 and S3P were associated with RA (p<0,05). Alleles S2 and/or S3P was present in 65% and 32% of patients in the control group (OR 3,86, p<0,001) and were associated with ACPA (OR 2.11, p=0,001). S3D alleles, S1, X showed a protective effect against RA. The results of this study demonstrate that Brazilian patients with RA from mostly mixed ethnicity, HLA-DRB1 evaluated under the hypothesis of the SE and the classification proposed by Du Montcel et al were associated with disease susceptibility and the presence of ACPA.

Os alelos HLA-DRB1, que codificam uma sequência de aminoácidos (QKRAA/QRRAA/RRRAA) nas posições 70 a 74 da terceira região hipervariável da cadeia &#61538;1 do gene DRB1, denominada epítopo compartilhado (EC), estão associados com maior susceptibilidade e gravidade para artrite reumatóide (AR) em diversas populações. Uma nova classificação proposta por Du Montcel et al tem sido desenvolvida para apurar a associação entre HLA-DRB1 e AR. Este estudo foi desenhado com o objetivo de determinar a frequência dos alelos HLA-DRB1 em pacientes brasileiros com AR, e sua associação com o fator reumatoide (FR), anticorpos antipeptídeos citrulinados (ACPA) e lesão radiográfica articular e óssea. Quatrocentos e doze pacientes com AR e 215 controles foram incluídos. A tipificação HLA-DRB1 foi realizada pela reação em cadeia de polimerase (PCR) usando primers específicos e hibridação com oligonucleotídeos de sequência específica (SSOP). A pesquisa de ACPA foi determinada pela técnica de ELISA e a do FR por nefelometria, a avaliação radiográfica realizada pelo método do índice de Sharp modificado de Van Der Heijde. Para análises estatísticas foram utilizados os testes do qui-quadrado, t de Student e a regressão logística. Nos pacientes com AR alelos HLA-DRB1*04:01, *04:04, *04:05 se associaram com AR (p<0,05), embora o amplo intervalo de confiança, vale a pena ressaltar a associação observada com o alelo DRB1*09:01 e a doença (p<0,05). Alelos HLA-DRB1 EC+ foram observados em 62,8% dos pacientes e em 31,1% do grupo controle (OR 3,62; p <0,001) e estiveram associados com ACPA (OR 2,03; p<0,001). Alelos DRB1 DERAA mostraram efeito protetor para a AR (OR 0,42; p<0,001). A análise da nova classificação de HLA-DRB1 mostra que S2 e S3P se associaram a AR (p<0,05). Alelos S2 e/ou S3P esteve presente em 65% dos pacientes e 32% do grupo controle (OR 3,86; p<0,001) e estiveram associados a ACPA (OR.2,11; p=0,001). Alelos S3D, S1, X mostraram efeito protetor para a AR. Os resultados obtidos neste estudo demonstram que pacientes brasileiros com AR de etnia majoritariamente mestiça, alelos HLA-DRB1 avaliados segundo a hipótese do EC e a classificação proposta por Du Montcel estiveram associados à suscetibilidade à doença e à presença de ACPA. / HLA-DRB1 alleles that encode an amino acid sequence at positions 70-74 of the third hypervariable region of the B chain of the DRB1 gene, called shared epitope (SE), are associated with increased susceptibility and severity to rheumatoid arthritis (RA) in different populations. A new classification proposed by Du Montcel et al has been developed to determine the association between HLA-DRB1 and RA. This study was designer to determine the frequency of HLA-DRB1 alleles in Brazilian patients with RA, and its association with rheumatoid factor (RF), citrullinated peptide antibodies (ACPA) and radiographic joint damage and bone. Four hundred and twelve patients with RA and 215 controls were included. The HLA-DRB1 typing was performed by polymerase chain reaction (PCR) using specific primers and hybridization with sequence specific oligonucleotides (SSOP). The survey of ACPA was determined by ELISA and the RF by nephelometry, the radiographic evaluation by index method modified Sharp Van Der Heijde. For statistical analysis we used the chi-square, Student and logistic regression. In patients with rheumatoid arthritis HLA-DRB1*04:01, *04:04, *04:05 are associated with RA (p<0,05), although the wide confidence interval, it is worth noting the association observed with the DRB1*09:01 allele and the disease (p<0,05). HLA-DRB1 SE+ were observed in 62.8% of patients and in 31.1% of the control group (OR 3.62, p<0,001) and were associated with ACPA (OR 2.03, p<0,001). DERRA alleles showed a protective effect against RA (OR 0,42, p<0,001). The analysis of the new classification of HLA-DRB1 shows that S2 and S3P were associated with RA (p<0,05). Alleles S2 and/or S3P was present in 65% and 32% of patients in the control group (OR 3,86, p<0,001) and were associated with ACPA (OR 2.11, p=0,001). S3D alleles, S1, X showed a protective effect against RA. The results of this study demonstrate that Brazilian patients with RA from mostly mixed ethnicity, HLA-DRB1 evaluated under the hypothesis of the SE and the classification proposed by Du Montcel et al were associated with disease susceptibility and the presence of ACPA.

Submitted by Lúcia Brandão (lucia.elaine@live.com) on 2015-12-11T19:01:49Z No. of bitstreams: 1 Dhêmerson - Dhêmerson Souza de Lima.pdf: 2134258 bytes, checksum: 027d2a19329c1030eb634da31db37ae6 (MD5) / Approved for entry into archive by Divisão de Documentação/BC Biblioteca Central (ddbc@ufam.edu.br) on 2016-01-19T14:57:53Z (GMT) No. of bitstreams: 1 Dhêmerson - Dhêmerson Souza de Lima.pdf: 2134258 bytes, checksum: 027d2a19329c1030eb634da31db37ae6 (MD5) / Approved for entry into archive by Divisão de Documentação/BC Biblioteca Central (ddbc@ufam.edu.br) on 2016-01-19T15:02:05Z (GMT) No. of bitstreams: 1 Dhêmerson - Dhêmerson Souza de Lima.pdf: 2134258 bytes, checksum: 027d2a19329c1030eb634da31db37ae6 (MD5) / Made available in DSpace on 2016-01-19T15:02:05Z (GMT). No. of bitstreams: 1 Dhêmerson - Dhêmerson Souza de Lima.pdf: 2134258 bytes, checksum: 027d2a19329c1030eb634da31db37ae6 (MD5) Previous issue date: 2015-05-08 / CAPES - Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / Tuberculosis (TB) is a serious public health problem, considered as a priority by the government of Brazil since 2003. This disease is endemic in low and middle-income countries, mainly affecting the population living in urban peripheries when associated with poor living conditions, malnutrition and drug abuse. Brazil is one of 22 countries contributing to the global high TB burden; it is on 16th position in number of TB cases. In 2014, Amazonas state had the highest national incidence rate of TB (68.4 per 100.000 inhabitants). Poverty, social exclusion, operational difficulties for diagnosis and treatment of TB are crucial to maintaining the high rate of incidence. In addition, the host immunogenic factors are associated with TB. Human Leukocyte Antigen (HLA) genes are associated with susceptibility or resistance to TB. This study verifies the frequency of HLA-DRB1*04 allele and subtypes in 622 subjects (316 patients with pulmonary TB and 306 controls). HLA-DRB1*04 was more frequent in TB patients (187/316; 59,2%) than control group (101/306; 33,0%). In this study, nine subtypes of HLA-DRB1*04 were identified. The subtype HLA-DRB1*04:11:01 was associated with susceptibility to pulmonary TB (p = 0.0019; OR = 2.23; 95% CI = 1.34 to 3.70), while HLA-DRB1*04:07:01 was associated with protection (p < 0.0001; OR = 0.02; 95% CI = 0.001 to 0.33) and HLA-DRB1*04:92 was associated with transmission to pulmonary TB disease (p = 0.0112; OR = 8.62; 95% CI = 1.63 to 45.5). These results suggest three subtypes of HLA-DRB1*04 as potential immunogenetic markers in TB and can help in better understanding of mechanisms involved in disease, as well as the reasons for high rates of TB incidence in Amazonas state. / A tuberculose (TB) é um grave problema de saúde pública, considerada como prioridade pelo governo do Brasil desde 2003. A doença é endêmica nos países de baixa e média renda, acometendo principalmente a população que reside nas periferias urbanas (favelas e invasões), estando associada às más condições de moradia, à alimentação, ao saneamento básico e ao uso de drogas. O Brasil é um dos 22 países que contribuem com as maiores cargas de TB no mundo, ocupando a 16.a posição em número absoluto de casos. O Estado do Amazonas, em 2014, apresentou o maior coeficiente de incidência nacional de casos de TB (68,4 por 100 mil habitantes). Miséria, exclusão social, dificuldades operacionais de diagnósticos e tratamento da TB são preponderantes para manutenção da alta taxa de incidência. Além disso, os fatores imunogenéticos do hospedeiro são descritos e associados à suscetibilidade ou à resistência da doença. Dentre os genes mais fortemente associados à TB, estão os do Antígeno Leucocitário Humano (HLA). No presente estudo, foi investigada a frequência do alelo HLA-DRB1*04 em 622 indivíduos, 316 pacientes com TB pulmonar e 306 controles. O HLA-DRB1*04 foi frequente nos pacientes (187/316; 59,2%), quando comparado aos dados dos controles (101/306; 33,0%). Neste estudo, foram identificados nove subtipos de HLADRB1*04; destes, o HLA-DRB1*04:11:01 foi associado à suscetibilidade (p = 0,0019; OR =2,23; IC 95% = 1,34 – 3,70) e à transmissão de TB pulmonar, enquanto o HLA-DRB1*04:07:01 foi associado à proteção (p < 0,0001; OR = 0,02; IC 95% = 0,001 – 0,33), e o HLA-DRB1*04:92 foi associado à transmissão da doença (p = 0,0112; OR = 8,62; IC 95% = 1,63 – 45,5). Esses resultados sugerem três subtipos do HLA-DRB1*04 como potenciais marcadores imunogenéticos na TB, os quais podem ajudar na compreensão dos mecanismos envolvidos na doença, bem como esclarecer os motivos das altas taxas de incidência de TB no Estado do Amazonas.

京都大学 / 新制・課程博士 / 博士(医学) / 甲第23773号 / 医博第4819号 / 新制||医||1057(附属図書館) / 京都大学大学院医学研究科医学専攻 / (主査)教授 金子 新, 教授 杉田 昌彦, 教授 松田 秀一 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

Kidney failure is an important cause of morbidity and mortality, frequently associated with chronic inflammation of glomeruli and immune hypersensitivity reactions. In this study we aimed to determine if there was an association between HLA alleles and end stage kidney diseases. Towards this objective, we analyzed 87 patients with an average age of 51 years and a mean of 4.5 years of hemodialysis. The main clinical diagnosis of kidney failure in this group was hypertension (38%), diabetes (25%) and glomerulopathies (23%). As a control, we utilized the HLA typing data of 17,541 voluntary marrow donors from the Brazilian national registry. HLA typing was determined by SSO kits (One Lambda, Inc.) and flow cytometry (Luminex technology). Our results demonstrated that, when compared to the normal population, there was a significant association of: 1) hypertension with HLA-A*23 (p=0.014), HLA-A*30 (p<0.001) and HLA-B*41 (p=0.016); 2) diabetes with HLA-A*23 (p=0.004), HLA-A*30 (p=0.033), HLA-B*41 (p=0.023), HLA-B*81 (p=0.020), HLADRB 1*1 (p=0.030) and HLA-DRB1*3 (p=0.013); and 3) glomerulopathies with HLA-A*32 (p<0.001), HLA-B*13 (p<0.001), HLA-B*14 (p=0.004), HLA-DRB1*4 (p=0.030), HLADRB 1*11 (p=0.008) and HLA-DRB1*15 (p<0.001). There was an association between allele frequency and protection against kidney disease in the following situations: 1) hypertension with HLA-A*3 and HLA-DRB1*4; 2) diabetes with HLA-DRB1*11; 3) glomerulopathies with HLA-DRB1*1 and HLA-DRB1*13. In conclusion, HLA alleles may be an important marker of prognosis in chronic renal disease. / A insuficiência renal, frequentemente associada com inflamação glomerular crônica e com reações de hipersensibilidade, é importante causa de morbidade e mortalidade. O objetivo deste estudo foi determinar se havia associação entre alelos HLA e doença renal crônica terminal. Foram analisados 87 pacientes com idade média de 51 anos e realizando hemodiálise há, em média, 4,5 anos. Os principais diagnósticos clínicos da insuficiência renal neste grupo foram hipertensão (38%), diabetes (25%) e glomerulopatias (23%). Como controle foram utilizados dados de tipagens de HLA de 17.541 doadores voluntários de medula óssea do registro nacional Brasileiro. A tipagem de HLA foi determinada através de kits SSO (One Lambda, Inc) e citometria de fluxo (tecnologia Luminex). Nossos resultados demonstraram que, quando comparado com a população normal, havia associação significativa de: 1) hipertensão com HLA-A*23 (p=0,014), HLA-A*30 (p<0,001) e HLAB* 41 (p=0,016); 2) diabetes com HLA-A*23 (p=0,004), HLA-A*30 (p=0,033), HLA-B*41 (p=0,023), HLA-B*81 (p=0,020), HLA-DRB1*1 (p=0,030) e HLA-DRB1*3 (p=0,013); 3) glomerulopatias com HLA-A*32 (p<0,001), HLA-B*13 (p<0,001), HLA-B*14 (p=0,004), HLA-DRB1*4 (p=0,030), HLA-DRB1*11 (p=0,008) e HLA-DRB1*15 (p<0,001). Houve associação entre a frequência de alelos e proteção contra doença renal nas seguintes situações: 1) hipertensão com HLA-A*3 e HLA-DRB1*4; 2) diabetes com HLA-DRB1*11; 3) glomerulopatias com HLA-DRB1*1 e HLA-DRB1*13. Conclusão: alelos HLA podem ser importantes marcadores do prognóstico em doença renal crônica. / Doutor em Imunologia e Parasitologia Aplicadas

Syfte: Målet med denna studie var att undersöka ett möjligt samband mellan de olika HLA-DRB1*-allelerna med mängden Mutans Streptococci (MS) i saliven, med fokus på HLA DRB1*04, i en grupp förskolebarn i södra Sverige, Skåne.Material och metod: Salivprover från 318 HLA-DRB1*-typade barn odlades på MSB-agarplattor och antalet MS CFU räknades. Resultaten analyserades statistiskt med chi-två-test.Resultat: Inget signifikant samband kunde fastställas mellan någon av DRB1*04-allelerna och mängden MS. Dock var höga MS-värden ungefär dubbelt så vanligt för homozygota DRB1*04 alleler (p = 0,354). Höga MS-värden var vanligare för DRB1*04:01 allelen (p = 0,717). Däremot var höga MS-värden procentuellt mycket mindre förekommande för DRB1*04:04 allelen (p = 0,098). Ett statistisk signifikant samband (p = 0,003) kunde ses för pojkar positiva för DRB1*07:01-allelen. Höga MS-värden var mycket vanligare för DRB1*07:01-allelen.Slutsats: Ett samband mellan HLA-DRB1-alleler och mängden MS i saliven kan finnas. Resultaten indikerar att barn positiva för DRB1*04:01-allelen och homozygota DRB1*04-alleler har en tendens att uppvisa ett högre MS-värde i saliven jämfört med barn negativa för allelen. HLA-typen är antagligen bara en av många faktorer som påverkar mängden MS. Resultaten från denna studie är delvis i linje med tidigare studier och ytterligare studier behövs. / Objective: The aim of the study was to investigate a possible relationship of the different HLA-DRB1* alleles, with focus on HLA-DRB1*04, and the amount of Mutans Streptococci (MS) in saliva from a group of preschool children in the Southern part of Sweden, in the County of Skåne.Material and method: Saliva samples from 318 HLA-DRB1* typed children were cultivated on MSB agar and CFU of MS was counted. The results were statistically analyzed using chi-square tests.Results: No statistical significant relationship could be established between any DRB1*04 allele and the amount of MS. However, high numbers of MS was found to be about twice as common for homozygote DRB1*04 alleles (p = 0.364). High numbers of MS was more common for DRB1*04:01 alleles (p = 0.717). On the contrary, high levels of MS was much less common for DRB1*04:04 alleles (p = 0.098). A statistical significant relationship (p = 0.003) could be seen for boys positive for the DRB1*07:01 allele. High MS count was much more common for DRB1*07:01 alleles.Conclusion: A relationship between HLA-DRB1 alleles and the amount MS in the saliva might exist. The results indicate that children positive for the DRB1*04:01 allele and homozygote DRB1*04 alleles have a tendency to display more MS in their saliva compared to children negative to the alleles. The HLA type might just be one of many factors affecting the amount of MS. The results are partly in line with earlier studies and further studies are needed.

Indiana University-Purdue University Indianapolis (IUPUI) / Background: Bacterial adherence to the acquired dental pellicle, important in caries, is mediated by receptor-adhesin interactions such as Streptococcus mutans antigen I/II (I/II). Ten I/II epitopes from the A, V, P and C regions were chosen to determine their reactivity in human saliva. Underlying the body’s ability to immunologically respond to bacteria that lead to caries are the human leukocyte antigen (HLA) genes, specifically HLA class II (HLA-II) genes that control antigen presentation. Previous studies suggested that a specific HLA biomarker group (HLA-DRB1*04) may have differential control of immune responses to I/II. However, it was not known whether secretory IgA (SIgA) responses to the selected epitopes from HLA-DRB1*04 positive subjects were different compared to their non-biomarker counterparts (negative), or across other caries factors, since no study to date had thus assessed these questions. Methods: Per IRB approval, the study population was divided into age, sex and race matched DRB1*04 positive (n=16) and negative groups (n=16). SIgA-epitope (and whole cell) reactivity was determined using ELISA. Other caries factors were measured. Subjects received a clinical exam by a trained examiner. ix Differences between DRB1*04 positive and negative groups were examined using a two-sided, two-sample t-test. Results: DRB1*04 positive subjects had numerically, but not statistically, higher reactivity to 9 out of 10 epitopes, the exception being residues 834-853 from the V and P regions of I/II across multiple measures. Though statistically insignificant, DRB1*04 positive subjects also exhibited 25-30 μg mL-1 less total IgA (TIgA) than negative counterparts. All clinical caries data proved inconclusive when comparing groups, likely due to exogenous factors and sample size. Conclusion: DRB1*04 positive subjects showed a trend toward lower TIgA. Moreover, they also showed a lower SIgA response across multiple measures to 834-853, the I/II V and P region epitope. This region forms a sort of functional epicenter involved in collaboration between domains along the entire I/II antigen, and governs the region involved in initial attachment to the acquired dental pellicle. This region may be involved in an in vivo discontinuous conformationally specific immunogenic epitope that serves as an HLA-II binding motif which remains elusive.