Bio

Professional Education


  • Doctor of Philosophy, University Of Helsinki (2012)
  • Master of Science, University Of Jyvaskyla (2007)

Stanford Advisors


Publications

Journal Articles


  • HLA-DPB1 and HLA Class I Confer Risk of and Protection from Narcolepsy. American journal of human genetics Ollila, H. M., Ravel, J., Han, F., Faraco, J., Lin, L., Zheng, X., Plazzi, G., Dauvilliers, Y., Pizza, F., Hong, S., Jennum, P., Knudsen, S., Kornum, B. R., Dong, X. S., Yan, H., Hong, H., Coquillard, C., Mahlios, J., Jolanki, O., Einen, M., Lavault, S., Högl, B., Frauscher, B., Crowe, C., Partinen, M., Huang, Y. S., Bourgin, P., Vaarala, O., Désautels, A., Montplaisir, J., Mack, S. J., Mindrinos, M., Fernandez-Vina, M., Mignot, E. 2015; 96 (1): 136-146

    Abstract

    Type 1 narcolepsy, a disorder caused by a lack of hypocretin (orexin), is so strongly associated with human leukocyte antigen (HLA) class II HLA-DQA1(?)01:02-DQB1(?)06:02 (DQ0602) that very few non-DQ0602 cases have been reported. A known triggering factor for narcolepsy is pandemic 2009 influenza H1N1, suggesting autoimmunity triggered by upper-airway infections. Additional effects of other HLA-DQ alleles have been reported consistently across multiple ethnic groups. Using over 3,000 case and 10,000 control individuals of European and Chinese background, we examined the effects of other HLA loci. After careful matching of HLA-DR and HLA-DQ in case and control individuals, we found strong protective effects of HLA-DPA1(?)01:03-DPB1(?)04:02 (DP0402; odds ratio [OR] = 0.51 [0.38-0.67], p = 1.01 × 10(-6)) and HLA-DPA1(?)01:03-DPB1(?)04:01 (DP0401; OR = 0.61 [0.47-0.80], p = 2.07 × 10(-4)) and predisposing effects of HLA-DPB1(?)05:01 in Asians (OR = 1.76 [1.34-2.31], p = 4.71 × 10(-05)). Similar effects were found by conditional analysis controlling for HLA-DR and HLA-DQ with DP0402 (OR = 0.45 [0.38-0.55] p = 8.99 × 10(-17)) and DP0501 (OR = 1.38 [1.18-1.61], p = 7.11 × 10(-5)). HLA-class-II-independent associations with HLA-A(?)11:01 (OR = 1.32 [1.13-1.54], p = 4.92 × 10(-4)), HLA-B(?)35:03 (OR = 1.96 [1.41-2.70], p = 5.14 × 10(-5)), and HLA-B(?)51:01 (OR = 1.49 [1.25-1.78], p = 1.09 × 10(-5)) were also seen across ethnic groups in the HLA class I region. These effects might reflect modulation of autoimmunity or indirect effects of HLA class I and HLA-DP alleles on response to viral infections such as that of influenza.

    View details for DOI 10.1016/j.ajhg.2014.12.010

    View details for PubMedID 25574827

  • HLA DQB1*06:02 Negative Narcolepsy with Hypocretin/Orexin Deficiency SLEEP Han, F., Lin, L., Schormair, B., Pizza, F., Plazzi, G., Ollila, H. M., Nevsimalova, S., Jennum, P., Knudsen, S., Winkelmann, J., Coquillard, C., Babrzadeh, F., Strom, T. M., Wang, C., Mindrinos, M., Vina, M. F., Mignot, E. 2014; 37 (10): 1601-1608

    View details for DOI 10.5665/sleep.4066

    View details for Web of Science ID 000343147400006

  • Dual Cases of Type 1 Narcolepsy with Schizophrenia and Other Psychotic Disorders JOURNAL OF CLINICAL SLEEP MEDICINE Canellas, F., Lin, L., Rosa Julia, M., Clemente, A., Vives-Bauza, C., Ollila, H. M., Hong, S. C., Arboleya, S. M., Einen, M. A., Faraco, J., Fernandez-Vina, M., Mignot, E. 2014; 10 (9): 1011-1018

    Abstract

    Cases of narcolepsy in association with psychotic features have been reported but never fully characterized. These patients present diagnostic and treatment challenges and may shed new light on immune associations in schizophrenia.Our case series was gathered at two narcolepsy specialty centers over a 9-year period. A questionnaire was created to improve diagnosis of schizophrenia or another psychotic disorder in patients with narcolepsy. Pathophysiological investigations included full HLA Class I and II typing, testing for known systemic and intracellular/synaptic neuronal antibodies, recently described neuronal surface antibodies, and immunocytochemistry on brain sections to detect new antigens.Ten cases were identified, one with schizoaffective disorder, one with delusional disorder, two with schizophreniform disorder, and 6 with schizophrenia. In all cases, narcolepsy manifested first in childhood or adolescence, followed by psychotic symptoms after a variable interval. These patients had auditory hallucinations, which was the most differentiating clinical feature in comparison to narcolepsy patients without psychosis. Narcolepsy therapy may have played a role in triggering psychotic symptoms but these did not reverse with changes in narcolepsy medications. Response to antipsychotic treatment was variable. Pathophysiological studies did not reveal any known autoantibodies or unusual brain immunostaining pattern. No strong HLA association outside of HLA DQB1*06:02 was found, although increased DRB3*03 and DPA1*02:01 was notable.Narcolepsy can occur in association with schizophrenia, with significant diagnostic and therapeutic challenges. Dual cases maybe under diagnosed, as onset is unusually early, often in childhood. Narcolepsy and psychosis may share an autoimmune pathology; thus, further investigations in larger samples are warranted.

    View details for DOI 10.5664/jcsm.4040

    View details for Web of Science ID 000341999700012

    View details for PubMedID 25142772

  • Genome wide analysis of narcolepsy in China implicates novel immune loci and reveals changes in association prior to versus after the 2009 H1N1 influenza pandemic. PLoS genetics Han, F., Faraco, J., Dong, X. S., Ollila, H. M., Lin, L., Li, J., An, P., Wang, S., Jiang, K. W., Gao, Z. C., Zhao, L., Yan, H., Liu, Y. N., Li, Q. H., Zhang, X. Z., Hu, Y., Wang, J. Y., Lu, Y. H., Lu, C. J., Zhou, W., Hallmayer, J., Huang, Y. S., Strohl, K. P., Pollmächer, T., Mignot, E. 2013; 9 (10)

    Abstract

    Previous studies in narcolepsy, an autoimmune disorder affecting hypocretin (orexin) neurons and recently associated with H1N1 influenza, have demonstrated significant associations with five loci. Using a well-characterized Chinese cohort, we refined known associations in TRA@ and P2RY11-DNMT1 and identified new associations in the TCR beta (TRB@; rs9648789 max P = 3.7 × 10(-9) OR 0.77), ZNF365 (rs10995245 max P = 1.2 × 10(-11) OR 1.23), and IL10RB-IFNAR1 loci (rs2252931 max P = 2.2 × 10(-9) OR 0.75). Variants in the Human Leukocyte Antigen (HLA)- DQ region were associated with age of onset (rs7744020 P = 7.9×10(-9) beta -1.9 years) and varied significantly among cases with onset after the 2009 H1N1 influenza pandemic compared to previous years (rs9271117 P = 7.8 × 10(-10) OR 0.57). These reflected an association of DQB1*03:01 with earlier onset and decreased DQB1*06:02 homozygosity following 2009. Our results illustrate how genetic association can change in the presence of new environmental challenges and suggest that the monitoring of genetic architecture over time may help reveal the appearance of novel triggers for autoimmune diseases.

    View details for DOI 10.1371/journal.pgen.1003880

    View details for PubMedID 24204295

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