A recessive major gene controls the mitsuda reaction in a region endemic for leprosy.
BACKGROUND
Leprosy is a chronic infectious disease caused by Mycobacterium leprae. The Mitsuda reaction is a delayed granulomatous skin reaction elicited by intradermal injection of heat-killed M. leprae. Interestingly, results of the Mitsuda test are positive in the majority of individuals, even in areas not endemic for M. leprae. Like leprosy, the Mitsuda reaction is thought to be genetically controlled, but its mode of inheritance is unknown, although the role of the NRAMP1 gene has previously been reported.


METHODS
We conducted a segregation analysis of quantitative Mitsuda reactivity in 168 Vietnamese nuclear families ascertained through patients with leprosy.


RESULTS
We found strong evidence (P<10-9) for a major gene controlling the Mitsuda reaction independently of leprosy clinical status. Subsequent linkage analysis showed that this major gene was distinct from NRAMP1. Under the major-gene model, approximately 12% of individuals are homozygous for the recessive predisposing allele and are predicted to display high levels of Mitsuda reactivity (mean, approximately 10 mm, versus 5 mm in other individuals).


CONCLUSIONS
We provide evidence that the Mitsuda reaction is controlled by a major gene. Our study paves the way for the identification of this gene and should provide novel insight into the mechanisms involved in granuloma formation, especially in M. leprae infection.
Ranque
Brigitte
B
Laboratoire de Genetique Humaine des Maladies Infectieuses, Universite de Paris Rene Descartes-INSERM U.550, Faculte de Medecine Necker, Paris, France, European Union.
Alcais
Alexandre
A
Thuc
Nguyen Van
NV
Woynard
Sebastien
S
Thai
Vu Hong
VH
Huong
Nguyen Thu
NT
Ba
Nguyen Ngoc
NN
Khoa
Pham Xuan
PX
Schurr
Erwin
E
Abel
Laurent
L
D005260:Female; D005808:Genes, Recessive; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D007271:Injections, Intradermal; D007916:Lepromin / Q000276:immunology*; D007918:Leprosy / Q000453:epidemiology* / Q000235:genetics / Q000276:immunology; D015440:Leprosy, Lepromatous / Q000276:immunology; D015441:Leprosy, Tuberculoid / Q000453:epidemiology / Q000235:genetics / Q000276:immunology; D008297:Male; D009166:Mycobacterium leprae / Q000235:genetics*; D012867:Skin / Q000276:immunology*; D014744:Vietnam
D007916:Lepromin