No description available.

No description available.

Alfuy virus (ALFV) is a member of the Japanese encephalitis virus (JEV) antigenic complex of flaviviruses and is currently classified as a subtype of Murray Valley encephalitis virus (MVEV). However, while MVEV and JEV pose significant health risks to regions of Northern Australia, there is little evidence that ALFV causes disease in humans or other animals. Due to the apparent low pathogenicity of ALFV, few studies have previously focused on this virus, therefore, very little is known about it. This thesis aims to improve our understanding of this virus, with the potential of using ALFV, or markers of attenuation discovered within its genome, to develop novel vaccines for use against MVEV, JEV, and even other members of the Flavivirus genus. Previously, nucleotide sequence analysis of a small portion of the genome of ALFV was used to reclassify the virus as a subtype of MVEV. During this project the entire genome of ALFV was sequenced and compared with other members of the genus. Phylogenetic relationships revealed that although ALFV is closely related to MVEV, it is no closer to MVEV than to JEV or to Usutu virus, suggesting that ALFV should not be classed as a subtype of MVEV. Indeed, antigenic studies comparing ALFV, MVEV and JEV, using mAbs produced to MVEV, show a distinct antigenic profile for ALFV. Several unique genetic markers that may affect the virulence of ALFV were observed in the genome. Within the envelope (E) protein, the conserved Nlinked glycosylation motif contained a substitution causing a loss of glycosylation. Also within the E protein, the hinge region, involved in low-pH dependent conformational changes in the protein, also showed several amino acid differences when compared with MVEV and other related viruses. In addition, the highly conserved terminal dinucleotide was deleted. This region is thought to be important for replication of viral RNA. Virulence studies of different strains of ALFV in three-week old Swiss outbred mice also show a different pattern of virulence to MVEV. While MVEV is highly neurovirulent and neuroinvasive in these animals, ALFV exhibits weak neuroinvasiveness, producing very little disease in mice infected intraperitoneally, and producing ALFV-specific antibody only in mice infected with high doses. Even in the highly susceptible IFN-alphaR-/- mice (deficient in the receptor for interferon-alpha), ALFV caused significantly delayed mortality. This data suggests that ALFV is inefficient at replicating in the periphery of these animals. ALFV also exhibited a different tropism to MVEV in vitro, showing significantly reduced replication in Vero cells, a line of African Green Monkey kidney cells that supports efficient replication of all other members of the JEV complex. Binding studies showed that ALFV was able to bind to the surface of these cells, but electroporation of viral RNA directly into the cytoplasm was unable to initiate infection, suggesting inefficient replication or translation of ALFV viral RNA in this cell type. To determine the motifs responsible for these unique phenotypic characteristics of ALFV, three chimeric viruses were engineered based on a previously constructed infectious clone of MVEV. One, containing the structural (prM and E) genes of ALFV in the MVEV backbone, exhibited weak neuroinvasiveness, similar to ALFV, but unlike ALFV, was able to replicate efficiently in Vero cells, and produced ALFVspecific antibody in mice infected with low viral doses. This suggests that the structural genes of ALFV are associated with poor neuroinvasion, but are not responsible for poor extraneural replication in mice, or lack of growth in Vero cells. Another mutant virus was constructed by deleting the terminal dinucleotide in the MVEV infectious clone. This clone spontaneously reverted to the wild type sequence, preventing phenotypic analysis of this mutation. The final chimera contained the nonstructural genes of ALFV with the structural genes and the UTRs of MVEV. Unfortunately, despite several attempts, this clone was unstable in the bacterial host, and insertions or deletions were spontaneously introduced into the genome. Based on phylogenetic, antigenic and virulence data, ALFV is sufficiently different from MVEV to be classified as a separate virus within the genus. Determinants of the low neuroinvasiveness of ALFV have been localized to the structural genes of ALFV, probably within the hinge region of E, and/or due to the lack of glycosylation of the E protein. The cause of the delayed growth in Vero cells was unable to be determined, but is not due to a motif within the structural genes.

Alfuy virus (ALFV) is a member of the Japanese encephalitis virus (JEV) antigenic complex of flaviviruses and is currently classified as a subtype of Murray Valley encephalitis virus (MVEV). However, while MVEV and JEV pose significant health risks to regions of Northern Australia, there is little evidence that ALFV causes disease in humans or other animals. Due to the apparent low pathogenicity of ALFV, few studies have previously focused on this virus, therefore, very little is known about it. This thesis aims to improve our understanding of this virus, with the potential of using ALFV, or markers of attenuation discovered within its genome, to develop novel vaccines for use against MVEV, JEV, and even other members of the Flavivirus genus. Previously, nucleotide sequence analysis of a small portion of the genome of ALFV was used to reclassify the virus as a subtype of MVEV. During this project the entire genome of ALFV was sequenced and compared with other members of the genus. Phylogenetic relationships revealed that although ALFV is closely related to MVEV, it is no closer to MVEV than to JEV or to Usutu virus, suggesting that ALFV should not be classed as a subtype of MVEV. Indeed, antigenic studies comparing ALFV, MVEV and JEV, using mAbs produced to MVEV, show a distinct antigenic profile for ALFV. Several unique genetic markers that may affect the virulence of ALFV were observed in the genome. Within the envelope (E) protein, the conserved Nlinked glycosylation motif contained a substitution causing a loss of glycosylation. Also within the E protein, the hinge region, involved in low-pH dependent conformational changes in the protein, also showed several amino acid differences when compared with MVEV and other related viruses. In addition, the highly conserved terminal dinucleotide was deleted. This region is thought to be important for replication of viral RNA. Virulence studies of different strains of ALFV in three-week old Swiss outbred mice also show a different pattern of virulence to MVEV. While MVEV is highly neurovirulent and neuroinvasive in these animals, ALFV exhibits weak neuroinvasiveness, producing very little disease in mice infected intraperitoneally, and producing ALFV-specific antibody only in mice infected with high doses. Even in the highly susceptible IFN-alphaR-/- mice (deficient in the receptor for interferon-alpha), ALFV caused significantly delayed mortality. This data suggests that ALFV is inefficient at replicating in the periphery of these animals. ALFV also exhibited a different tropism to MVEV in vitro, showing significantly reduced replication in Vero cells, a line of African Green Monkey kidney cells that supports efficient replication of all other members of the JEV complex. Binding studies showed that ALFV was able to bind to the surface of these cells, but electroporation of viral RNA directly into the cytoplasm was unable to initiate infection, suggesting inefficient replication or translation of ALFV viral RNA in this cell type. To determine the motifs responsible for these unique phenotypic characteristics of ALFV, three chimeric viruses were engineered based on a previously constructed infectious clone of MVEV. One, containing the structural (prM and E) genes of ALFV in the MVEV backbone, exhibited weak neuroinvasiveness, similar to ALFV, but unlike ALFV, was able to replicate efficiently in Vero cells, and produced ALFVspecific antibody in mice infected with low viral doses. This suggests that the structural genes of ALFV are associated with poor neuroinvasion, but are not responsible for poor extraneural replication in mice, or lack of growth in Vero cells. Another mutant virus was constructed by deleting the terminal dinucleotide in the MVEV infectious clone. This clone spontaneously reverted to the wild type sequence, preventing phenotypic analysis of this mutation. The final chimera contained the nonstructural genes of ALFV with the structural genes and the UTRs of MVEV. Unfortunately, despite several attempts, this clone was unstable in the bacterial host, and insertions or deletions were spontaneously introduced into the genome. Based on phylogenetic, antigenic and virulence data, ALFV is sufficiently different from MVEV to be classified as a separate virus within the genus. Determinants of the low neuroinvasiveness of ALFV have been localized to the structural genes of ALFV, probably within the hinge region of E, and/or due to the lack of glycosylation of the E protein. The cause of the delayed growth in Vero cells was unable to be determined, but is not due to a motif within the structural genes.

Alfuy virus (ALFV) is a member of the Japanese encephalitis virus (JEV) antigenic complex of flaviviruses and is currently classified as a subtype of Murray Valley encephalitis virus (MVEV). However, while MVEV and JEV pose significant health risks to regions of Northern Australia, there is little evidence that ALFV causes disease in humans or other animals. Due to the apparent low pathogenicity of ALFV, few studies have previously focused on this virus, therefore, very little is known about it. This thesis aims to improve our understanding of this virus, with the potential of using ALFV, or markers of attenuation discovered within its genome, to develop novel vaccines for use against MVEV, JEV, and even other members of the Flavivirus genus. Previously, nucleotide sequence analysis of a small portion of the genome of ALFV was used to reclassify the virus as a subtype of MVEV. During this project the entire genome of ALFV was sequenced and compared with other members of the genus. Phylogenetic relationships revealed that although ALFV is closely related to MVEV, it is no closer to MVEV than to JEV or to Usutu virus, suggesting that ALFV should not be classed as a subtype of MVEV. Indeed, antigenic studies comparing ALFV, MVEV and JEV, using mAbs produced to MVEV, show a distinct antigenic profile for ALFV. Several unique genetic markers that may affect the virulence of ALFV were observed in the genome. Within the envelope (E) protein, the conserved Nlinked glycosylation motif contained a substitution causing a loss of glycosylation. Also within the E protein, the hinge region, involved in low-pH dependent conformational changes in the protein, also showed several amino acid differences when compared with MVEV and other related viruses. In addition, the highly conserved terminal dinucleotide was deleted. This region is thought to be important for replication of viral RNA. Virulence studies of different strains of ALFV in three-week old Swiss outbred mice also show a different pattern of virulence to MVEV. While MVEV is highly neurovirulent and neuroinvasive in these animals, ALFV exhibits weak neuroinvasiveness, producing very little disease in mice infected intraperitoneally, and producing ALFV-specific antibody only in mice infected with high doses. Even in the highly susceptible IFN-alphaR-/- mice (deficient in the receptor for interferon-alpha), ALFV caused significantly delayed mortality. This data suggests that ALFV is inefficient at replicating in the periphery of these animals. ALFV also exhibited a different tropism to MVEV in vitro, showing significantly reduced replication in Vero cells, a line of African Green Monkey kidney cells that supports efficient replication of all other members of the JEV complex. Binding studies showed that ALFV was able to bind to the surface of these cells, but electroporation of viral RNA directly into the cytoplasm was unable to initiate infection, suggesting inefficient replication or translation of ALFV viral RNA in this cell type. To determine the motifs responsible for these unique phenotypic characteristics of ALFV, three chimeric viruses were engineered based on a previously constructed infectious clone of MVEV. One, containing the structural (prM and E) genes of ALFV in the MVEV backbone, exhibited weak neuroinvasiveness, similar to ALFV, but unlike ALFV, was able to replicate efficiently in Vero cells, and produced ALFVspecific antibody in mice infected with low viral doses. This suggests that the structural genes of ALFV are associated with poor neuroinvasion, but are not responsible for poor extraneural replication in mice, or lack of growth in Vero cells. Another mutant virus was constructed by deleting the terminal dinucleotide in the MVEV infectious clone. This clone spontaneously reverted to the wild type sequence, preventing phenotypic analysis of this mutation. The final chimera contained the nonstructural genes of ALFV with the structural genes and the UTRs of MVEV. Unfortunately, despite several attempts, this clone was unstable in the bacterial host, and insertions or deletions were spontaneously introduced into the genome. Based on phylogenetic, antigenic and virulence data, ALFV is sufficiently different from MVEV to be classified as a separate virus within the genus. Determinants of the low neuroinvasiveness of ALFV have been localized to the structural genes of ALFV, probably within the hinge region of E, and/or due to the lack of glycosylation of the E protein. The cause of the delayed growth in Vero cells was unable to be determined, but is not due to a motif within the structural genes.

No description available.

Les bilharzioses hépatospléniques sont des maladies parasitaires provoquées essentiellement par Schistosoma japonicum et Schistosoma mansoni. Ces infections provoquent une fibrose hépatique sévère chez 5 à 20% des sujets infectées vivant en zone endémique. Plusieurs études ont démontré que le développement de cette fibrose était régulé par des cytokines et chemokines et que la susceptibilité génétique à cette maladie dépendait chez l'homme d'un locus majeur sur le chromosome humain 6 en position q23. L'IL-22 est une cytokine produite essentiellement par les lymphocytes T auxiliaires et les cellules NK et qui a été impliqué dans la protection du foie et de l'intestin chez la souris. Le gène IL22RA2 codant pour le récepteur inhibiteur soluble de l'IL-22 (IL-22BP) est localisé dans la région de susceptibilité à la FH (6q23). Nous avons donc étudié l'implication de l'IL-22 dans la pathologie bilharzienne par une approche immunogénétique. Notre étude démontre que la production d'IL-22 est augmentée en réponse aux œufs de S. japonicum et aux antigènes d'œufs de S. mansoni dans des cultures de cellules mononuclées du sang périphérique d'individus chinois et brésiliens vivant dans des zones endémiques. Le traitement par le Praziquantel, qui favorise l'élimination des parasites et la réversion de la fibrose, est associé à une augmentation des taux d'IL-22 en culture. Nous avons observé que dans le sang des patients chinois, l'IL-22 est produit majoritairement par les lymphocytes T CD4+ et des cellules CD3-CD4- ne produisant pas d'IL-17A. Les taux d'IL-22 en culture et la proportion des cellules CD3-CD4-IL22+ sont inversement corrélés à la FH. / Hepatosplenic schistosomiasis is a parasitic disease caused primarily by Schistosoma japonicum and Schistosoma mansoni. These infections cause severe hepatic fibrosis (HF) in 5-20% of infected subjects living in endemic areas. Several studies have shown that the development of this fibrosis was regulated by cytokines and chemokines. Our laboratory has shown that genetic susceptibility to HF map to a major locus on human chromosome 6 at position q23. IL-22 is a cytokine produced primarily by T cells and NK cells and has been involved in protecting the liver and intestine in mice. The gene IL22RA2, encoding the soluble inhibitor receptor of IL-22 (IL-22BP), is located in the region of susceptibility to HF (6q23). We therefore examined the involvement of IL-22 in schistosomiasis pathology by an immunogenetic approach. Our study shows that the production of IL-22 is increased in response to eggs of S. japonicum and egg antigens of S. mansoni in cultures of peripheral blood mononuclear cells from Chinese and Brazilian subjects living in endemic areas. Treatment with praziquantel, which helps eliminate parasites and reversion of HF, is associated with increased levels of IL-22 in culture. We observed that in the blood of Chinese patients, IL-22 is produced mainly by CD4+ T cells and CD3-CD4-cells that do not produce IL-17A. The levels of IL-22 in culture and the proportion of CD3+CD4-IL22+ are inversely correlated with HF. These observations suggest that IL-22 may play a protective role in HF. To confirm this implication, we performed association studies between SNPs located in IL22 and IL22RA2 genes and HF.

Neutrophils are significant players in both acute and chronic inflammatory conditions, and function in infectious and autoimmune ailments. MicroRNAs regulate homeostasis in health and disease by fine tuning the expression of a network of genes through post transcriptional regulation. Many microRNAs are expressed in restricted tissues, regulated by physiological conditions such as stress and disease, and are emerging as mediators for intercellular communication that shape the tissue environments. MicroRNA profiles have been recently utilized as biomarkers for diagnosis and prognostic purposes for their stability in plasma and significant correlation with the disease progress. In addition, several microRNAs are in clinical trials for infectious diseases, cardiovascular disorders and cancer. As for neutrophil biology, microRNAs that regulate hematopoiesis and neutrophil development are well known. However, only a few microRNAs are characterized in the context of neutrophil migration and activation by loss of function studies either in mice or in cell culture. In this work we characterize the role of total microRNA regulation on neutrophil function through whole body and neutrophil specific Dicer1 knockout, and identify a microRNA regulator of neutrophil motility. MiR-722 downregulates the transcript level of rac2 through binding to a seed match in the rac2 3'UTR. Furthermore, miR-722 over-expressing larvae display improved outcomes in both sterile and bacterial systemic models. Finally, the miR-722 mimics protect zebrafish from lethal LPS challenge, providing evidence and mechanism of an anti-inflammatory microRNA that restrains detrimental systemic inflammation. We further investigated the role of the inflammatory response in an ischemia-reperfusion model. Extensive future work is required, especially in animal models, to illustrate the pivotal and complex microRNA mediated regulatory network in neutrophils, which is expected to provide the foundation for highly selective microRNA based therapy to control neutrophil behavior in infection and inflammatory disorders.

O Lúpus Eritematoso Sistêmico (LES) é uma doença auto-imune caracterizada pela deposição de imunocomplexos nos tecidos. O clareamento de imunocomplexos está comprometido no LES, contribuindo para a patogênese da nefrite lúpica. Os receptores Fcg (FcgR) participam do clareamento dos imunocomplexos contendo IgG, pois se ligam à porção Fc desta molécula. O FcgRIIa é um receptor que tem dois alelos co-dominantemente expressos, o R131 e o H131, os quais diferem na sua eficiência em se ligar a subclasses de IgG. Células que expressam o homozigoto FcgRIIa-H/H131 são as únicas que se ligam eficientemente a imunocomplexos contendo IgG2, enquanto as que expressam FcgRIIa-R/R131 o fazem de forma menos eficaz. Este polimorfismo tem sido descrito como fator de risco para nefrite lúpica, embora ainda haja controvérsias. O propósito do nosso estudo foi o de analisar, em uma população de nefrite lúpica e em outra de glomerulopatias primárias, a associação entre o genótipo FcgRIIa-R/R131 e a gravidade da doença renal na sua instalação (definida pelo momento da biópsia renal) e ao final do seguimento, bem como possíveis relações com aspectos histológicos renais. A genotipagem do receptor FcgRIIa foi realizada em 76 pacientes com nefrite lúpica e 63 com glomerulopatias primárias através da extração do DNA genômico, seguido de reação de polimerização em cadeia (PCR) e nested PCR, utilizando-se primers específicos. Os pacientes foram avaliados por parâmetros clínicos e laboratoriais. Setenta e um pacientes com nefrite lúpica realizaram biópsia renal, enquanto 5 que já se encontravam em hemodiálise não a realizaram. Pacientes com glomerulonefrite membranoproliferativa, nefropatia da IgA e glomerulonefrite proliferativa mesangial foram agrupados como glomerulopatias proliferativas enquanto os com glomeruloesclerose segmentar e focal, glomerulopatia de lesões mínimas ou glomerulonefrite membranosa foram agrupados como glomerulopatias não proliferativas. O homozigoto FcgRIIa-R/R131 foi mais prevalente no grupo com nefrite lúpica (42,1% de R/R131 e 14,5% de H/H131) em relação ao grupo com glomerulopatias primárias (23,8% de R/R131 e 23,8% de H/H131), dado este estatisticamente significativo (p<0.05). Houve segregação do genótipo FcgRIIa- R/R131 nos pacientes com nefrite lúpica quando comparados aos com glomerulopatias não proliferativas, mas não quando comparados aos com glomerulopatias proliferativas (p<0.05). Não houve diferença na distribuição genotípica do receptor FcgRIIa em relação a classe histológica de nefrite lúpica, tampouco em relação aos que evoluíram ou não para insuficiência renal (Pcr = 1,4mg/dl ao final do seguimento). Um aumento na frequência do genótipo FcgRIIa- R/R131 foi encontrado nos pacientes com nefrite lúpica apresentando níveis mais elevados de FAN (FAN>1/100) e consumo de complemento C3 (p<0,05), mas não naqueles com presença de anticorpos anti-dsDNA ou anti-fosfolípide (p>0,05). Estes achados sugerem que uma distribuição anormal dos genótipos do receptor FcgRIIa com predomínio do homozigoto R/R131 é um fator importante que pode influenciar o desenvolvimento de nefrite lúpica e de glomerulopatias proliferativas. O genótipo FcgRIIa-R/R131 também está relacionado com maior atividade lúpica (FAN>1/100 e consumo de C3) em pacientes brasileiros. / Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by tissue deposition of immune complexes. Immune complex clearance is impaired in SLE, contributing to the pathogenesis of lupus nephritis. Fcg receptors (FcgR) participate in the clearance of the immune complexes containing immunoglobulin G, because they bind the Fc domain of this molecule. The FcgRIIa receptor has two co dominant alleles, R131 and H131. They differ in their efficiency to bind IgG subclasses. Cells expressing the homozygote FcgRIIa-H/H131 are the only ones, which bind efficiently immune complexes containing IgG2, whereas those expressing FcgRIIa-R/R131 do not. This polymorphism has been described as a risk factor for lupus nephritis. However, reports are still controversial. This study aims to establish the role of FcgRIIa polymorphism in the severity and prognosis of lupus nephritis compared to primary glomerulopathies, and whether it is related to histological findings or not. In 76 patients with lupus nephritis and 63 patients with primary glomerulopathies, genotyping of the FcgRIIa receptor was performed with standard PCR, followed by nested PCR using specific primers. The same patients were assessed according to clinical and laboratory patterns. Seventy-one patients with lupus nephritis underwent biopsy, while five did not since they were already under dialysis. Patients diagnosed as membranoproliferative glomerulonephritis, IgA glomerulonephritis and mesangial proliferative glomerulonephritis were grouped as proliferative glomerulopathies, while those with focal segmental glomerulosclerosis, membranous glomerulonephritis and minimal change disease were grouped as nonproliferative glomerulopathies. The homozygous FcgRIIa-R/R131 was more prevalent in lupus nephritis (42,1% being R/R131 and 14,5% H/H131) than in glomerulopathies (23,8% being R/R131 and 23,8% H/H131). These data were statistically significant (p<0.05). A segregation of the FcgRIIa-R/R131 genotype was found in patients with lupus nephritis compared to nonproliferative glomerulopathies, but not when compared to proliferative glomerulopathies (p<0.05). No relation was found between genotype distribution and histological class or renal insufficiency (end-study serum creatinine = 1.4 mg/dl). The genotype R/R131 was more prevalent in lupus nephritis patients presenting complement 3 (C3) consumption and higher antinuclear factor (ANF) titers, but not in those with antidouble- stranded DNA or antiphospholipid antibodies (p>0.05). We concluded that a skewed distribution of the FcgRIIa genotypes with R/R131 predominance may contribute to the development of lupus nephritis and proliferative glomerulopathy. In Brazilian patients, this polymorphism is also related to more intense lupus activity (ANF > 1/100 and C3 consumption).

O Lúpus Eritematoso Sistêmico (LES) é uma doença auto-imune caracterizada pela deposição de imunocomplexos nos tecidos. O clareamento de imunocomplexos está comprometido no LES, contribuindo para a patogênese da nefrite lúpica. Os receptores Fcg (FcgR) participam do clareamento dos imunocomplexos contendo IgG, pois se ligam à porção Fc desta molécula. O FcgRIIa é um receptor que tem dois alelos co-dominantemente expressos, o R131 e o H131, os quais diferem na sua eficiência em se ligar a subclasses de IgG. Células que expressam o homozigoto FcgRIIa-H/H131 são as únicas que se ligam eficientemente a imunocomplexos contendo IgG2, enquanto as que expressam FcgRIIa-R/R131 o fazem de forma menos eficaz. Este polimorfismo tem sido descrito como fator de risco para nefrite lúpica, embora ainda haja controvérsias. O propósito do nosso estudo foi o de analisar, em uma população de nefrite lúpica e em outra de glomerulopatias primárias, a associação entre o genótipo FcgRIIa-R/R131 e a gravidade da doença renal na sua instalação (definida pelo momento da biópsia renal) e ao final do seguimento, bem como possíveis relações com aspectos histológicos renais. A genotipagem do receptor FcgRIIa foi realizada em 76 pacientes com nefrite lúpica e 63 com glomerulopatias primárias através da extração do DNA genômico, seguido de reação de polimerização em cadeia (PCR) e nested PCR, utilizando-se primers específicos. Os pacientes foram avaliados por parâmetros clínicos e laboratoriais. Setenta e um pacientes com nefrite lúpica realizaram biópsia renal, enquanto 5 que já se encontravam em hemodiálise não a realizaram. Pacientes com glomerulonefrite membranoproliferativa, nefropatia da IgA e glomerulonefrite proliferativa mesangial foram agrupados como glomerulopatias proliferativas enquanto os com glomeruloesclerose segmentar e focal, glomerulopatia de lesões mínimas ou glomerulonefrite membranosa foram agrupados como glomerulopatias não proliferativas. O homozigoto FcgRIIa-R/R131 foi mais prevalente no grupo com nefrite lúpica (42,1% de R/R131 e 14,5% de H/H131) em relação ao grupo com glomerulopatias primárias (23,8% de R/R131 e 23,8% de H/H131), dado este estatisticamente significativo (p<0.05). Houve segregação do genótipo FcgRIIa- R/R131 nos pacientes com nefrite lúpica quando comparados aos com glomerulopatias não proliferativas, mas não quando comparados aos com glomerulopatias proliferativas (p<0.05). Não houve diferença na distribuição genotípica do receptor FcgRIIa em relação a classe histológica de nefrite lúpica, tampouco em relação aos que evoluíram ou não para insuficiência renal (Pcr = 1,4mg/dl ao final do seguimento). Um aumento na frequência do genótipo FcgRIIa- R/R131 foi encontrado nos pacientes com nefrite lúpica apresentando níveis mais elevados de FAN (FAN>1/100) e consumo de complemento C3 (p<0,05), mas não naqueles com presença de anticorpos anti-dsDNA ou anti-fosfolípide (p>0,05). Estes achados sugerem que uma distribuição anormal dos genótipos do receptor FcgRIIa com predomínio do homozigoto R/R131 é um fator importante que pode influenciar o desenvolvimento de nefrite lúpica e de glomerulopatias proliferativas. O genótipo FcgRIIa-R/R131 também está relacionado com maior atividade lúpica (FAN>1/100 e consumo de C3) em pacientes brasileiros. / Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by tissue deposition of immune complexes. Immune complex clearance is impaired in SLE, contributing to the pathogenesis of lupus nephritis. Fcg receptors (FcgR) participate in the clearance of the immune complexes containing immunoglobulin G, because they bind the Fc domain of this molecule. The FcgRIIa receptor has two co dominant alleles, R131 and H131. They differ in their efficiency to bind IgG subclasses. Cells expressing the homozygote FcgRIIa-H/H131 are the only ones, which bind efficiently immune complexes containing IgG2, whereas those expressing FcgRIIa-R/R131 do not. This polymorphism has been described as a risk factor for lupus nephritis. However, reports are still controversial. This study aims to establish the role of FcgRIIa polymorphism in the severity and prognosis of lupus nephritis compared to primary glomerulopathies, and whether it is related to histological findings or not. In 76 patients with lupus nephritis and 63 patients with primary glomerulopathies, genotyping of the FcgRIIa receptor was performed with standard PCR, followed by nested PCR using specific primers. The same patients were assessed according to clinical and laboratory patterns. Seventy-one patients with lupus nephritis underwent biopsy, while five did not since they were already under dialysis. Patients diagnosed as membranoproliferative glomerulonephritis, IgA glomerulonephritis and mesangial proliferative glomerulonephritis were grouped as proliferative glomerulopathies, while those with focal segmental glomerulosclerosis, membranous glomerulonephritis and minimal change disease were grouped as nonproliferative glomerulopathies. The homozygous FcgRIIa-R/R131 was more prevalent in lupus nephritis (42,1% being R/R131 and 14,5% H/H131) than in glomerulopathies (23,8% being R/R131 and 23,8% H/H131). These data were statistically significant (p<0.05). A segregation of the FcgRIIa-R/R131 genotype was found in patients with lupus nephritis compared to nonproliferative glomerulopathies, but not when compared to proliferative glomerulopathies (p<0.05). No relation was found between genotype distribution and histological class or renal insufficiency (end-study serum creatinine = 1.4 mg/dl). The genotype R/R131 was more prevalent in lupus nephritis patients presenting complement 3 (C3) consumption and higher antinuclear factor (ANF) titers, but not in those with antidouble- stranded DNA or antiphospholipid antibodies (p>0.05). We concluded that a skewed distribution of the FcgRIIa genotypes with R/R131 predominance may contribute to the development of lupus nephritis and proliferative glomerulopathy. In Brazilian patients, this polymorphism is also related to more intense lupus activity (ANF > 1/100 and C3 consumption).