Humoral responses to the measles, mumps and rubella vaccine are impaired in Leigh Syndrome French Canadian patients.

Adrien Fois,Christian Renaud,Christine Des Rosiers,Sylvie Lesage,Julie Thompson Legault,Charles Morin,Anne-Marie Boucher-Lafleur,Lise Coderre,Catherine Laprise,David Chau

doi:10.1371/journal.pone.0239860

Abstract

Leigh Syndrome French Canadian (LSFC) is a rare autosomal recessive metabolic disorder characterized by severe lactic acidosis crises and early mortality. LSFC patients carry mutations in the Leucine Rich Pentatricopeptide Repeat Containing (LRPPRC) gene, which lead to defects in the respiratory chain complexes and mitochondrial dysfunction. Mitochondrial respiration modulates cellular metabolic activity, which impacts many cell types including the differentiation and function of immune cells. Hence, we postulated that, in addition to neurological and metabolic disorders, LSFC patients may show impaired immune activity. To gain insight into the quality of the immune response in LSFC patients, we examined the response to the measles, mumps and rubella (MMR) vaccine by measuring antibody titers to MMR in the plasma. In a cohort of eight LSFC patients, the response to the MMR vaccine was variable, with some individuals showing antibodies to all three viruses, while others had antibodies to two or fewer viruses. These results suggest that the mutations in the LRPPRC gene present in LSFC patients may affect the immune response to vaccines. Monitoring vaccine response in this fragile population should be considered to ensure full protection against pathogens.

Highlights

Leigh Syndrome is a neurodegenerative disease that results from genetic mutations leading to mitochondrial dysfunction [1,2]
Vaccine response in a mitochondrial disorder ca/home-accueil-eng.aspx SL is a Research Scholars Emeritus awardee from the Fonds de recherche Quebec – Sante. http://www.frqs.gouv. qc.ca/en/ AF holds a scholarship from the Departement de microbiologie, infectiologie et immunologie at the University of Montreal. https:// microbiologie.umontreal.ca/ The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript
We opted to exploit Leigh Syndrome French Canadian (LSFC) patient plasma samples that were collected as part of a previous study, which aimed at characterizing the metabolic signature of these patients [13,14]

Summary

Introduction

Leigh Syndrome is a neurodegenerative disease that results from genetic mutations leading to mitochondrial dysfunction [1,2]. A variant of this disease, Leigh Syndrome French Canadian (LSFC), was first described in the Saguenay-Lac-Saint-Jean region of Quebec, where the prevalence is estimated to be 1 in 2000 births [3,4]. LSFC differs from the classical Leigh Syndrome in the occurrence of acute and unpredictable metabolic. Vaccine response in a mitochondrial disorder ca/home-accueil-eng.aspx SL is a Research Scholars Emeritus awardee from the Fonds de recherche Quebec – Sante. Qc.ca/en/ AF holds a scholarship from the Departement de microbiologie, infectiologie et immunologie at the University of Montreal. Https:// microbiologie.umontreal.ca/ The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript Vaccine response in a mitochondrial disorder ca/home-accueil-eng.aspx SL is a Research Scholars Emeritus awardee from the Fonds de recherche Quebec – Sante. http://www.frqs.gouv. qc.ca/en/ AF holds a scholarship from the Departement de microbiologie, infectiologie et immunologie at the University of Montreal. https:// microbiologie.umontreal.ca/ The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

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