Potential risk factors for multiple sclerosis in Rio de Janeiro: a case-control study.

PURPOSE. To evaluate potential risk factors for the development of multiple sclerosis in Brazilian patients. METHOD. A case control study was carried out in 81 patients enrolled at the Department of Neurology of the Hospital da Lagoa in Rio de Janeiro, and 81 paired controls. A standardized questionnaire on demographic, social and cultural variables, and medical and family history was used. Statistical analysis was performed using descriptive statistics and conditional logistic regression models with the SPSS for Windows software program. RESULTS. Having standard vaccinations (vaccinations specified by the Brazilian government) (OR=16.2; 95% CI=2.3-115.2), smoking (OR=7.6; 95% CI=2.1-28.2), being single (OR=4.7; 95% CI=1.4-15.6) and eating animal brain (OR=3.4; 95% CI=1.2-9.8) increased the risk of developing MS. CONCLUSIONS. RESULTS of this study may contribute towards better awareness of the epidemiological characteristics of Brazilian patients with multiple sclerosis.

Cervical myelopathy in hereditary multiple exostoses.

Spinal cord compression due to cervical exostoses is a rare but recognized complication of hereditary multiple exostosis (HME), an autosomal dominant disorder. This disease, also called multiple osteochondromatosis, is characterised by osteocartilaginous exostoses, typically involving the juxtaepiphyseal regions of long bones. Complications such as transformation to sarcoma (1 to 5%) or neurological compression (of the spinal cord, 1 to 9%) can arise during the course of the disease. We report the case of a 64-year-old man with progressive difficulties in walking over many years, ascribed to congenital rachitism. A diagnosis of HME was not made until late in the disease course. Investigations revealed cervical myelopathy due to vertebral exostosis as well as multiple exostoses in other sites. His gait was not improved after surgical decompression. A better knowledge of this disease could have prevented this neurological complication.

Neptune: a hil simulator for multiple UUVs

This paper overviews the field of graphical simulators used for AUV development, presents the taxonomy of these applications and proposes a classification. It also presents Neptune, a multivehicle, real-time, graphical simulator based on OpenGL that allows hardware in the loop simulations

Differential cognitive impairment for diverse forms of multiple sclerosis.

BACKGROUND Cognitive impairment is a common feature in multiple sclerosis (MS) patients and occurs in 60% of all cases. Unfortunately, neurological examination does not always agree with the neuropsychological evaluation in determining the cognitive profile of the patient. On the other hand, psychophysiological techniques such as event-related potentials (ERPs) can help in evaluating cognitive impairment in different pathologies. Behavioural responses and EEG signals were recorded during the experiment in three experimental groups: 1) a relapsing-remitting group (RRMS), 2) a benign multiple sclerosis group (BMS) and 3) a Control group. The paradigm employed was a spatial attention task with central cues (Posner experiment). The main aim was to observe the differences in the performance (behavioural variables) and in the latency and amplitude of the ERP components among these groups. RESULTS Our data indicate that both MS groups showed poorer task performance (longer reaction times and lower percentage of correct responses), a latency delay for the N1 and P300 component, and a different amplitude for the frontal N1. Moreover, the deficit in the BMS group, indexed by behavioural and pyschophysiological variables, was more pronounced compared to the RRMS group. CONCLUSION The present results suggest a cognitive impairment in the information processing in all of these patients. Comparing both pathological groups, cognitive impairment was more accentuated in the BMS group compared to the RMSS group. This suggests a silent deterioration of cognitive skills for the BMS that is not usually treated with pharmacological or neuropsychological therapy.

Analysis of selectin ligands supporting hematologic malignancy cell interactions with their microenvironment : focus on leukemia and multiple myeloma

CONTEXTE: Les sélectines sont une famille de trois protéines qui règlent la capture et le roulement des leucocytes et qui initient la cascade d'adhésion. Elles contrôlent également la migration des leucocytes en réponse à un stimulus physiologique ou inflammatoire pour atteindre un organe cible. Le rôle des sélectines et des leurs ligands est bien connu dans l'adhésion des leucocytes normaux à l'endothélium; en revanche, la nature des ligands des sélectines exprimés par les cellules leucémiques et le myélome multiple est peu connue. La récente découverte que la E- et la P-sélectine sont exprimées par les cellules endothéliales et du stroma de la moelle osseuse, nous a incité à examiner leur rôle dans les interactions des cellules malignes avec leur environnement médullaire. RÉSULTATS: Les analyses ont été conduites sur les cellules du sang ou de la moelle osseuse prélevées à des patients atteints de leucémie aiguë ou de myélome multiple et sur des lignées cellulaires. Les ligands des sélectines qui ont été identifiés sur les blastes leucémiques ou les plasmocytes, sont « P-selectin glycoprotein ligand-1 » (PSGL-1), CD44, CD43 et l'endoglycan (EGC), ainsi que les saccharides fucosylés sLex et CLA. Nous avons vérifié dans des expériences d'adhésion cellulaire effectuées dans des conditions de flux que ces ligands sont fonctionnels, étant porteurs des sucres mentionnés, et qu'ils sont capables de supporter le roulement cellulaire dépendant des sélectines. De plus, nous avons montré que la liaison de ces ligands génère des signaux intracellulaires favorisant la prolifération et la survie des cellules de myélome. CONCLUSION. Les données présentées ici montrent que la E- et la P- sélectine du microenvironnement médullaire interagissent avec les cellules leucémiques et de myélome multiple, et que ces interactions activent des voies de signalisation contrôlant la prolifération et la survie cellulaire. Ces effets protecteurs sont impliqués dans la persistance de clones cellulaires malins résistant aux traitements et peuvent conduire à la récidive de la maladie. L'inhibition de ces interactions pourrait fournir de nouvelles options thérapeutiques pour le traitement de ces maladies de mauvais pronostic. - BACKGROUND: Selectins are a family of glycoproteins involved in the first steps of the adhesion cascade, tethering and rolling, during which leukocytes sense tissue specific signals and commit the cells to enter in a particular organ or inflammation site. While the role of selectins and their ligands is well established in supporting normal leukocyte adhesion to vascular endothelium, our knowledge of selectin ligands in two hematological malignancies, acute leukemia and multiple myeloma, is incomplete. The recent discovery that E- and P- selectin are also expressed on bone marrow (BM) endothelial and stromal cells, prompted us to investigate a potential role in selectin-mediated interaction of malignant cells with its protective BM microenvironment. RESULTS. Using cells obtained from blood or BM of patients affected by acute myeloid or lymphoblastic leukemia, or multiple myeloma, as well as cell lines, we characterized the expression of selectin ligands on blasts and plasma cells and identified P-selectin glycoprotein ligand-1 (PSGL-1), CD44, CD43 and endoglycan (EGC), as well as sLex/CLA determinants. Rolling assays under flow conditions allowed us to verify that these ligands are functional, i.e. correctly glycosylated and able to support selectin-mediated rolling. Moreover, we demonstrated that these ligands trigger proliferation and pro-survival signals upon engagement on myeloma cells. CONCLUSIONS. Data presented here demonstrate that E- and P-selectin in the BM microenvironment interact with leukemia and myeloma cells, and suggest that they have an impact on proliferation and survival of malignant plasma cells. These protective effects may induce drug resistance in malignant clones, leading to disease relapse. Interfering with these interactions could provide new therapeutic options. - Le corps humain dépend du système immunitaire pour sa protection face aux agressions, notamment des bactéries ou des virus, ou face à une dysfonction de l'organisme. Ce système est composé de plusieurs types cellulaires, regroupés sous le nom de leucocytes, qui participent à son fonctionnement. Ces cellules se développent à partir d'une cellule souche hématopo'iétique commune qui réside dans la moelle osseuse. Comme c'est le cas dans les autres tissus, les cellules du système immunitaire peuvent aussi développer des cancers, appelés tumeurs hématopoïétiques ou tumeurs du sang. Bien que ces maladies puissent être traitées avec succès grâce à de fortes doses de chimiothérapies ou à d'autres moyens comme les greffes, les patients connaissent un fort taux de rechute. La raison de ces récidives est la survie d'une partie des cellules malignes dans la moelle osseuse, où elles reçoivent une protection au traitement par le biais de l'interaction avec d'autres cellules. Les sélectines (E-, P- et L-sélectine) régulent l'interaction des leucocytes avec l'endothélium (la paroi des vaisseaux sanguins), d'autres leucocytes et les plaquettes ; ces interactions surviennent quand les leucocytes atteignent un site d'inflammation ou un organe cible. Dans la moelle osseuse, la E- et la P-sélectine se trouvent sur les cellules de l'endothélium et sur les macrophages, qui sont d'autres leucocytes faisant partie du stroma de la moelle. Elles pourraient être impliquées dans la protection des cellules cancéreuses évoquée plus haut. Les molécules d'adhésion avec lesquelles les sélectines s'associent, autrement dit les ligands des sélectines, sont des glycoprotéines. Ces protéines ont besoin de sucres spécifiques pour acquérir une telle capacité d'adhésion. Dans le cadre de cette thèse, nous avons étudié deux types de cellules extraites du sang et de la moelle osseuse des patients atteints d'une leucémie aiguë (les blastes) ou de myélome multiple (les plasmocytes), et leur capacité à se lier aux sélectines. Nous avons démontré une interaction entre ces cellules malignes et la E- et/ou la P-sélectine, à condition que les ligands soient correctement décorés. De plus, lors que les plasmocytes se lient aux sélectines, une cascade de signaux à l'intérieur des cellules stimule leur prolifération et leur survie. L'ensemble de ces résultats permet l'identification de nouvelles cibles thérapeutiques potentielles de ces hémopathies de mauvais pronostic.

Relation of cardiac troponin I measurements at 24 and 48 hours to magnetic resonance-determined infarct size in patients with ST-elevation myocardial infarction.

Levels of circulating cardiac troponin I (cTnI) or T are correlated to extent of myocardial destruction after an acute myocardial infarction. Few studies analyzing this relation have employed a second-generation cTnI assay or cardiac magnetic resonance (CMR) as the imaging end point. In this post hoc study of the Efficacy of FX06 in the Prevention of Mycoardial Reperfusion Injury (F.I.R.E.) trial, we aimed at determining the correlation between single-point cTnI measurements and CMR-estimated infarct size at 5 to 7 days and 4 months after a first-time ST-elevation myocardial infarction (STEMI) and investigating whether cTnI might provide independent prognostic information regarding infarct size at 4 months even taking into account early infarct size. Two hundred twenty-seven patients with a first-time STEMI were included in F.I.R.E. All patients received primary percutaneous coronary intervention within 6 hours from onset of symptoms. cTnI was measured at 24 and 48 hours after admission. CMR was conducted within 1 week of the index event (5 to 7 days) and at 4 months. Pearson correlations (r) for infarct size and cTnI at 24 hours were r = 0.66 (5 days) and r = 0.63 (4 months) and those for cTnI at 48 hours were r = 0.67 (5 days) and r = 0.65 (4 months). In a multiple regression analysis for predicting infarct size at 4 months (n = 141), cTnI and infarct location retained an independent prognostic role even taking into account early infarct size. In conclusion, a single-point cTnI measurement taken early after a first-time STEMI is a useful marker for infarct size and might also supplement early CMR evaluation in prediction of infarct size at 4 months.

A novel study of copy number variations in Hirschsprung disease using the multiple ligation-dependent probe amplification (MLPA) technique.

BACKGROUND Hirschsprung disease (HSCR) is a congenital malformation of the hindgut produced by a disruption in neural crest cell migration during embryonic development. HSCR has a complex genetic etiology and mutations in several genes, mainly the RET proto-oncogene, have been related to the disease. There is a clear predominance of missense/nonsense mutations in these genes whereas copy number variations (CNVs) have been seldom described, probably due to the limitations of conventional techniques usually employed for mutational analysis. METHODS In this study we have aimed to analyze the presence of CNVs in some HSCR genes (RET, EDN3, GDNF and ZFHX1B) using the Multiple Ligation-dependent Probe Amplification (MLPA) approach. RESULTS Two alterations in the MLPA profiles of RET and EDN3 were detected, but a detailed inspection showed that the decrease in the corresponding dosages were due to point mutations affecting the hybridization probes regions. CONCLUSION Our results indicate that CNVs of the gene coding regions analyzed here are not a common molecular cause of Hirschsprung disease. However, further studies are required to determine the presence of CNVs affecting non-coding regulatory regions, as well as other candidate genes.

Pulmonary Sarcoid-like Granulomatosis after Multiple Vaccinations of a Long-term Surviving Patient with Metastatic Melanoma.

Autoimmune side effects are frequent in patients with cancer treated with immune checkpoint-targeting antibodies, but are rare with cancer vaccines. Here, we present a case report on a patient with metastatic melanoma who developed pulmonary sarcoid-like granulomatosis following repetitive vaccinations with peptides and CpG. Despite multiple metastases, including one lesion in the brain, the patient is alive and well more than 13 years after the diagnosis of metastatic disease. The strongly activated tumor-specific CD8(+) T cells showed robust long-term memory and effector functions. It is possible that long-term survival and adverse autoimmune events may become more common for vaccines inducing robust anticancer immune responses as were present in this patient. Cancer Immunol Res; 2(12); 1148-53. ©2014 AACR.

Social evolution and defences against pathogens in ants

Pathogens represent a threat to all organisms, which generates a coevolutionary arms race. Social insects provide an interesting system to study host-pathogen interactions, because their defences depend on both the individual and collective responses, and involve genetic, physiological, behavioral and organizational mechanisms. In this thesis, I studied the evolutionary ecology of the resistance of ant queens and workers to natural fungal pathogens. Mechanisms that increase within-colony genetic diversity, like polyandry and polygyny, decrease relatedness among colony mates, which reduces the strength of selection for the evolution and maintenance of altruistic behavior. A leading hypothesis posits that intracolonial genetic diversity is adaptive because it reduces the risk of pathogen transmission. In chapter 1, I examine individual resistance in ant workers of Formica selysi, a species that shows natural variation in colony queen number. I discuss how this variation might be beneficial to resist natural fungal pathogens in groups. Overall my results indicate that there is genetic variation for fungal resistance in workers, a requirement for the 'genetic diversity for pathogen resistance' hypothesis. However I was not able to detect direct evidence that group diversity improves the survival of focal ants or reduces pathogen transmission. Thus, although the coexistence of multiple queens increases the within-colony variance in worker resistance, it remains unclear whether it protects ant colonies from pathogens and whether it is comparable to polyandry in other social insects. Traditionally, it was thought that the immune system of invertebrates lacked memory and specificity. In chapter 2, I investigate individual immunity in ant queens and show that they may be able to adjust their pathogen defences in response to their current environment by means of immune priming, which bears similarities with the adaptive immunity of vertebrates. However, my results indicate that the expression of immune priming in ant queens may be influenced by factors like mating status, mating conditions or host species. In addition, I showed that mating increases pathogen resistance in çhe two ant species that I studied (F. selysi and Lasius niger). This raises the question of how ant queens invest heavily in both maintenance and reproduction, which I discuss in the context of the evolution of social organization. In chapter 3,1 investigate if transgenerational priming against a fungal pathogen protects the queen progeny. I failed to detect this effect, and discuss why the detection of transgenerational immune priming in ants is a difficult task. Overall, this thesis illustrates some of the individual and collective mechanisms that likely played a role in allowing ants to become one of the most diverse and ecologically successful groups of organisms. -- Les pathogènes représentent une menace pour tous les organismes, ce qui a engendré l'évolution d'une course aux armements. Les insectes sociaux sont un système intéressant permettant d'étudier les interactions hôtes-pathogènes, car leurs défenses dépendent de réponses aussi bien individuelles que collectives, et impliquent des mécanismes génétiques, physiologiques, comportementaux et organisationnels. Dans cette thèse, j'ai étudié l'écologie évolutive de la résistance des reines et des ouvrières de fourmis exposées à des champignons pathogènes. Les facteurs augmentant la diversité génétique à l'intérieur de la colonie, comme la polyandrie et la polygynie, diminuent la parenté, ce qui réduit la pression de sélection pour l'évolution et la maintenance des comportements altruistes. Une hypothèse dominante stipule que la diversité génétique à l'intérieur de la colonie est adaptative car elle réduit le risque de transmission des pathogènes. Dans le chapitre 1, nous examinons la résistance individuelle à des pathogènes fongiques chez les ouvrières de Formica selysi, une espèce présentant une variation naturelle dans le nombre de reines par colonie. Nous discutons aussi de la possibilité que ces variations individuelles augmentent la capacité du groupe à résister à des champignons pathogènes. Dans l'ensemble, nos résultats indiquent une variation génétique dans la résistance aux champignons chez les ouvrières, un prérequis à l'hypothèse que la diversité génétique du groupe augmente la résistance aux pathogènes. Cependant, nous n'avons pas pu détecter une preuve directe que la diversité du groupe augmente la survie de fourmis focales ou réduise la transmission des pathogènes. Ainsi, bien que la coexistence de plusieurs reines augmente la variance dans la résistance des ouvrières à l'intérieur de la colonie, la question de savoir si cela protège les colonies de fourmis contre les pathogènes et si cela est comparable à la polyandrie chez d'autres insectes sociaux reste ouverte. Traditionnellement, il était admis que le système immunitaire des invertébrés ne possédait pas de mémoire et était non-spécifique. Dans le chapitre 2, nous avons étudié l'immunité individuelle chez des reines de fourmis. Nous avons montré que les reines pourraient être capables d'ajuster leurs défenses contre les pathogènes en réponse à leur environnement, grâce à une pré-activation du système immunitaire (« immune priming ») ressemblant à l'immunité adaptative des vertébrés. Cependant, nos résultats indiquent que cette pré-activation du système immunitaire chez les reines dépend du fait d'être accouplée ou non, des conditions d'accouplement, ou de l'espèce. De plus, nous avons montré que l'accouplement augmente la résistance aux pathogènes chez les deux espèces que nous avons étudié (F. selysi et Lasius niger). Ceci pose la question de la capacité des reines à investir fortement aussi bien dans la maintenance que dans la reproduction, ce que nous discutons dans le contexte de l'évolution de l'organisation sociale. Dans le chapitre 3, nous étudions si la pré-activation trans-générationelle du système immunitaire [« trans-generational immune priming ») protège la progéniture de la reine contre un champignon pathogène. Nous n'avons par réussi à détecter cet effet, et discutons des raisons pour lesquelles la détection de la pré-activation trans-générationelle du système immunitaire chez les fourmis est une tâche difficile. Dans l'ensemble, cette thèse illustre quelques-uns des mécanismes individuels et collectifs qui ont probablement contribué à la diversité et à l'important succès écologique des fourmis.

On-pump beating heart coronary surgery for high risk patients requiring emergency multiple coronary artery bypass grafting.

BACKGROUND: Cardiopulmonary bypass (CPB) with aortic cross-clamping and cardioplegic arrest remains the method of choice for patients requiring standard myocardial revascularization. Therefore, very high-risk patients presenting with acute coronary syndrome, unstable angina, onset of cardiac decompensation and requiring emergency multiple myocardial revascularization, can have a poor outcome. The on-pump beating heart technique can reduce the mortality and the morbidity in such a selected group of patients and this report describes our clinical experience. METHODS: Out of 290 patients operated for CABG from January 2005 to January 2006, 25 (8.6%) selected high-risk patients suffering from life threatening coronary syndrome (mean age 69 +/- 7 years) and requiring emergency multiple myocardial revascularization, underwent on-pump beating heart surgery. The mean pre-operative left ventricle ejection fraction (LVEF) was 27 +/- 8%. The majority of them (88%) suffered of tri-vessel coronary disease and 6 (24%) had a left main stump disease. Nine patients (35%) were on severe cardiac failure and seven among them (28%) received a pre-operative intra-aortic balloon pump. The pre-operative EuroScore rate was equal or above 8 in 18 patients (73%). RESULTS: All patients underwent on-pump-beating heart coronary revascularization. The mean number of graft/patient was 2.9 +/- 0.6 and the internal mammary artery was used in 23 patients (92%). The mean CPB time was 84 +/- 19 minutes. Two patients died during the recovery stay in the intensive care unit, and there were no postoperative myocardial infarctions between the survivors. Eight patients suffered of transitorily renal failure and 1 patient developed a sternal wound infection. The mean hospital stay was 12 +/- 7 days. The follow-up was complete for all 23 patients survived at surgery and the mean follow-up time was 14 +/- 5 months. One patient died during the follow-up for cardiac arrest and 2 patients required an implantable cardiac defibrillator. One year after surgery they all had a standard trans-thoracic echocardiogram showing a mean LVEF rate of 36 +/- 11.8%. CONCLUSION: Standard on-pump arrested heart coronary surgery has higher mortality and morbidity in emergencies. The on-pump beating heart myocardial revascularization seems to be a valid alternative for the restricted and selected cohort of patients suffering from life threatening coronary syndrome and requiring multiple emergency CABG.

Multiple insecticide resistance in Aedes aegypti (Diptera: Culicidae) populations compromises the effectiveness of dengue vector control in French Guiana

In French Guiana, pyrethroids and organophosphates have been used for many years against Aedes aegypti. We aimed to establish both the resistance level of Ae. aegypti and the ultra low volume spray efficacy to provide mosquito control services with practical information to implement vector control and resistance management. Resistance to deltamethrin and fenitrothion was observed. In addition, the profound loss of efficacy of AquaK'othrine® and the moderate loss of efficacy of Paluthion® 500 were recorded. Fenitrothion remained the most effective candidate for spatial application in French Guiana until its removal in December 2010. Further investigation of the mechanism of resistance to deltamethrin demonstrated the involvement of mixed-function oxidases and, to a lesser extent, of carboxylesterases. However, these observations alone cannot explain the level of insecticide resistance we observed during tube and cage tests.

Multiple cytokine expression profiles reveal immune-based differences in occult hepatitis B genotype H-infected Mexican Nahua patients

A high prevalence of occult hepatitis B (OHB) genotype H infections has been observed in the native Mexican Nahua population. In addition, a low incidence of hepatitis B virus (HBV)-associated hepatocellular carcinoma has been described in Mexico. The immune response to infection among OHB-infected patients has been poorly evaluated in vivo. Therefore, we assessed the expression profiles of 23 cytokines in OHB genotype H-infected Nahua patients. A total of 41 sera samples from natives of the Nahua community were retrospectively analysed. Based on their HBV antibody profiles, patients were stratified into two groups: OHB patients (n = 21) and patients that had recovered from HBV infection (n = 20). Herein, we report distinctive cytokines profiles in OHB-infected individuals. Compared to healthy controls (n = 20) and patients who resolved HBV infection, OHB-infected patients displayed an increase in interleukin (IL)-2 secretion in addition to a characteristic inflammation profile (decrease in IL-8 and tumour necrosis factor-alpha levels and increased levels of tumour growth factor-beta). IL-15 and interferon-gamma levels were reduced in OHB-infected individuals when compared to those patients who resolved HBV infection. In contrast, OHB patients showed an increase in monocyte chemoattractant protein (MCP)-1 and MCP-2 compared to healthy controls and patients who resolved HBV infection. These findings suggest that cytokine expression can influence the severity of OHB disease and could lead to new investigation into the treatment of liver and other infectious diseases.

Adherence to interferon β-1b treatment in patients with multiple sclerosis in Spain

BACKGROUND Adherence to interferon β-1b (INFβ-1b) therapy is essential to maximize the beneficial effects of treatment in multiple sclerosis (MS). For that reason, the main objectives of this study are to assess adherence to INFβ-1b in patients suffering from MS in Spain, and to identify the factors responsible for adherence in routine clinical practice. METHODOLOGY/PRINCIPAL FINDINGS This was an observational, retrospective, cross-sectional study including 120 Spanish patients with MS under INFβ-1b treatment. Therapeutic adherence was assessed with Morisky-Green test and with the percentage of doses received. The proportion of adherent patients assessed by Morisky-Green test was 68.3%, being indicative of poor adherence. Nevertheless, the percentage of doses received, which was based on the number of injected medication, was 94.3%. The main reason for missing INFβ-1b injections was forgetting some of the administrations (64%). Therefore, interventions that diminish forgetfulness might have a positive effect in the proportion of adherent patients and in the percentage of doses received. In addition, age and comorbidities had a significant effect in the number of doses injected per month, and should be considered in the management of adherence in MS patients. CONCLUSION/SIGNIFICANCE Among all the available methods for assessing adherence, the overall consumption of the intended dose has to be considered when addressing adherence.

DRB1*03:01 haplotypes: differential contribution to multiple sclerosis risk and specific association with the presence of intrathecal IgM bands.

BACKGROUND Multiple sclerosis (MS) is a multifactorial disease with a genetic basis. The strongest associations with the disease lie in the Human Leukocyte Antigen (HLA) region. However, except for the DRB1*15:01 allele, the main risk factor associated to MS so far, no consistent effect has been described for any other variant. One example is HLA-DRB1*03:01, with a heterogeneous effect across populations and studies. We postulate that those discrepancies could be due to differences in the diverse haplotypes bearing that allele. Thus, we aimed at studying the association of DRB1*03:01 with MS susceptibility considering this allele globally and stratified by haplotypes. We also evaluated the association with the presence of oligoclonal IgM bands against myelin lipids (OCMB) in cerebrospinal fluid. METHODS Genotyping of HLA-B, -DRB1 and -DQA1 was performed in 1068 MS patients and 624 ethnically matched healthy controls. One hundred and thirty-nine MS patients were classified according to the presence (M+, 58 patients)/absence (M-, 81 patients) of OCMB. Comparisons between groups (MS patients vs. controls and M+ vs. M-) were performed with the chi-square test or the Fisher exact test. RESULTS Association of DRB1*03:01 with MS susceptibility was observed but with different haplotypic contribution, being the ancestral haplotype (AH) 18.2 the one causing the highest risk. Comparisons between M+, M- and controls showed that the AH 18.2 was affecting only M+ individuals, conferring a risk similar to that caused by DRB1*15:01. CONCLUSIONS The diverse DRB1*03:01-containing haplotypes contribute with different risk to MS susceptibility. The AH 18.2 causes the highest risk and affects only to individuals showing OCMB.