ISHII, Yasuo

KUSAKA, Yukinori

MORIHIRO, Hironori

SATO, Kazuhiro

UEDA, Keiichi

YANAGIHARA, Makoto

ZHANG, Qunwei

University of Fukui Repository

SHORT COMMUNICATIONS  Contact  Dermatitis 1996: 34: 295
  Investigation of the association between mercury sensitization  and HLA-DR6 
 KAzuHIRO  SATOI, YUKINORI  KUSAKA  I,  QIJNWEI  ZHANG', MAKOTO YANAGIHARA2, KEIICHI UEDA2, 
 HIRONORI  MORIHIR03 AND YASUO  ISHII3 
     Departments  of 'Environmental  Health,  2Dermatology and  3Denta! Surgery, Fukui Medical School, 
                              Matsuoka-cho, Fukui  910-11, Japan 
Key  words. mercury sensitization; patch test; HLA-DR; epidemiology;  immunological b sis; genetic basis, © Munks-
gaard, 1996.
HLA molecules, polymorphic membrane glycoproteins, 
are classified into 2 groups: those expressed on the sur-
face of almost all nucleated cells  (HLA class I  mol-
ecules), and those found on the surface of cells mainly 
involved in the immune response  (HLA, class H mol-
ecules) (1). In guinea  pigs and mice, the genes that con-
trol delayed hypersensitivity reactions have been shown 
to be linked with those  of the major histocompatibility 
antigens (2). The immune response genes (Ia) of mice 
have their homologues in the human HLA-DR locus. 
Although significant increases in  HLA-DRw6 antigen in 
nickel-contact-sensitive patients have been reported (3), 
other attempts to investigate the link between HLA typ-
ing and metal contact sensitivity have resulted in con-
flicting results for nickel, cobalt and chromium  (I). 
However, there have been no reports of previous investi-
gations of the association between mercury sensitization 
and  HLA-DR. 
 Previously (4), we investigated various factors related 
to mercury sensitization  of 156, 4th year medical stu-
dents between 1993 and 1994. We found that mercury-
sensitized students had a significantly higher frequency 
of eczema caused by cosmetics, shampoos, soaps and 
hair creams, and had significantly more teeth modified 
with metals compared to controls. In addition, their uri-
nary mercury concentrations were significantly higher 
than those of the non-sensitized group. However, mer-
cury sensitization was not significantly associated with
Table 1. Results of serological HLA-DR typing in mercury-
sensitized subjects (n=20), with reference to non-sensitized con-
trols  (n=22) and the general Japanese population  (n=898)
Type I allergic  diseases. In the present study, we exam-
ined 215, 4th year students in 1995 and investigated vari-
ous factors relating to mercury  sensitization. We also 
performed serological HLA-DR typing of 20  mercury-
sensitized and 22 non-sensitized students as controls in 
the present study. 
 The rateof mercury sensitization was 13.0% (281215). 
The prevalences of HLA-DR types in the mercury-sensi-
tized and non-sensitized students in this study and in the 
general Japanese population (5) are summarized in 
Table  I. We found an increase in DR6 among the present 
subjects. However, there were no significant differences 
in incidence of any  of the HLA-DR types between mer-
cury-sensitized and non-sensitized students or the gen-
eral Japanese population (by the  , test). 
 Although we found an increase in DR6, there were 
no significant differences in any of the HLA-DR types 
between the 2 groups. Therefore, we could not reach a 
definitive conclusion with regard to DR antigens. If a 
definite association of  HLA type was found with metal 
sensitivity, preventive methods (e.g., antigen exclusion 
therapy) could be used from childhood in subjects who 
had the HLA type. More extensive r search is needed to 
clarify the associations between HLA types and metal 
sensitivity by using DNA sequence assays.
           No. Hg-
HLA-DR sensitized 
antigens students (%)
  No. Hg No. general 
non-sensitized Japanese 
students (%) population (%)
 DR1 
DR2 
DR3 
DR4 
DR5 
DR6 
DR7 
 DRS 
 DR9 
 DR10
1 (5) 
9 (45) 
 0 (0) 
7 (35) 
3 (15) 
9 (45) 
1 (5) 
1 (5) 
4 (20) 
0 (0)
2  (9_1) 
8 (36.4) 
1 (4.5) 
9 (40.9) 
3  (13.6) 
6  (2.7.3) 
0 (0) 
 4 (18.2) 
6 (27.3) 
1  (4.5)
96  (10.7) 
300  (33.4) 
 4 (0.4) 
363 (40.4) 
167  (l8.6) 
231 (25.7) 
 7 (0.8) 
223 (24,8) 
218 (24.3) 
 11  (1.2)
               References 
1. Emtestam L, Zetterquist H, Olerup  0.  HLA-DR, -DQ 
  and  -DP alleles in nickel, chromium,  and/or cobalt-sensi-
  tive individuals: genomic analysis based  on restriction  frag-
  ment length  polymorphisrns.  J Invest  Derniutol 1993: 100: 
  271-274. 
2. Polak  L, Barnes J M, Turk L. The genetic ontrol  of 
  contact  sensitization to inorganic metal compounds in 
  guinea pigs.  Immunology 1968:  14.-  707-711_ 
3.  Mozzanica N,  Rizzolo L,  Vemeroni G,  Diotti R, Hepeisen 
 S,  Finzi A  F B, C and DR antigens in nickel con-
  tact sensitivity. Br  J  Dermaiol 1990:  122: 309-313. 
4. Sato K, Kusaka Y,  Yanagihara M, Ueda K,  Mori T,  1v1i-
  yakosni  S. An epidemiologic study  of factors relating to 
  mercury sensitization.  Jpn  .1  Allergy 1995:  44:  86-92. 
5.  Imanishi T, Akaza T, Kimura A,  Tokunaga K, Gojobori T. 
  HLA 1991. Proceedings of  the  11th  International  Ilistocont-
 pliability Workshop and  Conference, vol. 1. Tsuji K, Aizawa 
  M, Sasazaki T (eds): Oxford: Oxford Science  Publications, 
  1991: 1065-1220.


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