Gene polymorphisms of mannose-binding lectin confer susceptibility to Pneumocystis pneumonia in HIV-infected patients.
BACKGROUND
Mannose-binding lectin (MBL) plays an important role in innate immunity. The aim of this study was to determine whether genetic variants of MBL confer susceptibility to Pneumocystis pneumonia (PCP) in patients with advanced human immunodeficiency virus (HIV) infections.


OBJECTIVE
HIV patients (n = 53) having CD4 counts <200/μL who were admitted to our hospital were analyzed. Of these 53 patients, 30 had PCP at admission, and 23 did not. Genotypes at six single nucleotide polymorphisms (SNP) in MBL2 gene and serum MBL levels were determined for each patient, and compared between patients with or without PCP. We also examined whether MBL enhances phagocytosis of macrophages against rat-type Pneumocystis organism in vitro.


RESULTS
Genotypes associated with low production of MBL were significantly more common in the PCP group than in the non-PCP group (P = 0.049, odds ratio 2.17, 95% CI 1.02-4.63). Serum MBL levels were significantly higher in the non-PCP group (P = 0.039). Findings from in vitro experiments indicated that MBL act as a direct opsonin enhancing macrophage-mediated phagocytosis of Pneumocystis organisms.


CONCLUSIONS
Genetic variation of MBL production influences susceptibility to PCP in patients with advanced HIV infection, and can be regarded as a risk factor for PCP.
Gunma University Graduate School of Medicine, Department and Medicine and Clinical Science, Japan.
Kunio
K
Yanagisawa
Gunma University Graduate School of Medicine, Department and Medicine and Clinical Science, Japan. Electronic address: yo-ogawa@gunma-u.ac.jp.
Yoshiyuki
Y
Ogawa
Gunma University Graduate School of Medicine, Department and Medicine and Clinical Science, Japan.
Hideki
H
Uchiumi
Gunma University Graduate School of Medicine, Department and Medicine and Clinical Science, Japan.
Fumito
F
Gohda
Gunma University Graduate School of Medicine, Department and Medicine and Clinical Science, Japan.
Momoko
M
Mawatari
Gunma University Graduate School of Medicine, Department and Medicine and Clinical Science, Japan.
Takuma
T
Ishizaki
Gunma University Graduate School of Medicine, Department and Medicine and Clinical Science, Japan.
Takeki
T
Mitsui
Gunma University Hospital, Division of Blood Transfusion Service, Japan.
Akihiko
A
Yokohama
Gunma University Graduate School of Medicine, Department and Medicine and Clinical Science, Japan.
Hiroshi
H
Handa
Gunma University Hospital, Oncology Center, Japan.
Norifumi
N
Tsukamoto
Gunma University Graduate School of Medicine, Department and Medicine and Clinical Science, Japan.
Yoshihisa
Y
Nojima
D017088:AIDS-Related Opportunistic Infections / Q000453:epidemiology / Q000235:genetics*; D000328:Adult; D000368:Aged; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006790:Host-Parasite Interactions / Q000235:genetics*; D006801:Humans; D008297:Male; D037601:Mannose-Binding Lectin / Q000235:genetics*; D008875:Middle Aged; D045363:Pneumocystis carinii; D011020:Pneumonia, Pneumocystis / Q000453:epidemiology / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012189:Retrospective Studies; D055815:Young Adult
D037601:Mannose-Binding Lectin
Acquired immunodeficiency syndrome (AIDS); Gene polymorphism; Human immunodeficiency virus (HIV); Mannose-binding lectin (MBL); Pneumocystis pneumonia (PCP)