Autoantibodies to Mi-2 were originally defined by double immunodiffusion using calf thymus extract as the antigen and reported as the first specific serologic marker of DM [
22]. IP was applied and a target antigen complex was characterized [
16], which was later identified as nucleosome remodeling deacetylase complex (NuRD) [
23]. Clinically, most of the anti-Mi-2 positive patients are DM [
22,
24‐
26]; however, clinical characteristics associated with anti-Mi-2 have not been studied extensively due to limited availability of the immunoassays and relatively low prevalence in PM/DM. The present study, with a total of 33 anti-Mi-2 positive patients confirmed by IP, is the largest cohort in the literature with a detailed clinical analysis of anti-Mi-2 positive patients. Clinical features of anti-Mi-2 positive patients in this study were consistent with previous literature; they were mostly DM with typical skin manifestations, and low prevalence of ILD and malignancy [
24]. Initial CPK levels were higher in the anti-Mi-2 positive DM group compared with the negative group (Table
3, Figure
1B). However, they responded well to steroid treatment in general; CPK levels were reduced dramatically and normalized in many cases (Table
3, Figure
1C), consistent with the good prognosis reported in the literature [
24]. The high prevalence of anti-Mi-2 (35%) and the low prevalence of anti-synthetase antibodies (4%) in Mexican PM/DM cases was the most striking finding in the present study (Table
1) compared with MSAs in other ethnicities. Anti-Jo-1 which is the most common MSA in the majority of studies [
4,
19] was found only in 4% of the PM/DM patients (7% in the PM and 3% in the DM). The prevalence of anti-Mi-2 was 35% in PM/DM and was increased to 45% in DM patients (Table
1). Data on the prevalence of MSAs in Mexicans are limited to basically one cohort in Mesoamerican Mestizo from Mexico City and Guadalajara [
5,
6]. Our data are consistent with the study that reported a high prevalence of anti-Mi-2 and a low prevalence of anti-synthetase antibodies, in Mexican PM/DM [
6] (Table
4). A correlation of UV radiation with the development of DM and production of anti-Mi-2 antibodies has been reported [
6,
27]. The role of sunlight in anti-Mi-2 production through alterations in the expression, subcellular distribution, and/or metabolism of components of the Mi-2 antigens, has been suggested [
6]. Supporting this hypothesis, regulation of Mi-2 expression by UV through protein translation and stability has been shown [
28]. Although the high prevalence of anti-Mi-2 in Mexican PM/DM was interpreted in association with high UV radiation in the area [
6], the roles of genetic versus environmental factors responsible for the production of anti-Mi-2 are not fully understood. Data on MSAs in the Mexican population living in the US to compare with these data are very limited. One study reported 8% prevalence of anti-Mi-2 in Mexican American PM/DM cases in Texas [
4], which is not higher than other ethnicities and is lower than that of Mestizo living in Mexico [
6]. This may seem to be consistent with the role of environmental factors, in particular UV radiation in anti-Mi-2 antibody production. However, a significant difference in the prevalence of anti-Mi-2 in Mexico City versus Guadalajara, which have comparable UV radiation levels, was observed in two independent studies by Okada
et al. [
6] and in the present study (Table
4). A significant difference in the prevalence of anti-Mi-2 in PM/DM patients in Mexico City versus those in Guadalajara (43% versus 14%,
P = 0.0088, Table
4) was found in our study. Interestingly, a similar pattern of prevalence of anti-Mi-2 in Mexico City versus Guadalajara PM/DM cases (36% versus 13%,
P = 0.03 by Fisher's exact test based on our calculation, not shown or discussed in the original study [
6]) was also reported in a previous independent study [
6]. When data from the two studies were combined (see Table
4, row 'anti-Mi-2 in PM/DM, combined'), the prevalence of anti-Mi-2 in Mexico City versus Guadalajara patients was 41% versus 14% (
P < 0.0001) with no overlap in 95% CI. Despite relatively small numbers of DM in the present study, no overlap in 95% CI was seen in the prevalence of anti-Mi-2 in Mexico City versus Guadalajara patients (59% versus 15%,
P = 0.001) (Table
4, row anti-Mi-2 in DM). Very similar data from two independent studies and statistical difference with no overlap of 95% CI support the interpretation that the difference between the two cities/cohorts is real. Interestingly, the percentage of DM in PM/DM in the two locations is similar, approximately 79% in the previous study [
6] and 69% to 71% in the present study, indicating that the different prevalence of anti-Mi-2 is not a reflection of a difference in PM:DM ratios. These data suggest that anti-Mi-2 production is affected by undetermined differences in the two Mexico locations of genetic and/or environmental factors other than UV radiation alone. While environmental factors are poorly characterized, significant differences in genetic background of Mexican-Mestizo in the two locations have been reported [
29]. Y-chromosome short-tandem repeats-based admixture estimates of African: European: Amerindian in the Mexican-Mestizo population in Mexico City is 4%:46%:50% whereas that in Jalisco County (where Guadalajara is located), is 5%:67%:28%, indicating a higher percentage of Amerindian derived genes in Mexico City and European derived gene dominance in Jalisco County [
29]. This heterogeneous genetic background among Mexicans could also be an important issue when interpreting the reported low prevalence of anti-Mi-2 in Mexican-Americans [
4] as the admixture of Mexican Americans in Texas [
30] appears to be very similar to that of Jalisco County (Guadalajara) [
29] that also has a low prevalence of anti-Mi-2 (Table
4). Other environmental factors not characterized in the previous studies may also be important in an unexplained accumulation of patients with a specific MSA to a certain year or geographical location, which does not appear to be due to genetic heterogeneity [
10,
11].
Table 4
Comparison of percentage of DM, prevalence of anti-Mi-2 and genetic origin in the literature
PM/DM number | 36 | 67 (46 DM) | 38 | 28 (20 DM) | 25 |
% of DM in PM/DM | 79% | 69% | 79% | 71% | NA |
Anti-Mi-2 in PM/DM (95% CI) | 36%a (20.8 to 53.8) | 43%b, c (31.2 to 56.0) | 13%a (4.4 to 28.1) | 14%b (4.0 to 32.7) | 8%c (1.0 to 26.0) |
Anti-Mi-2 in PM/DM, combined (95% CI) | 41%d, e (31.2 to 50.9) | 14%d (6.4 to 24.3) | 8%e (1.0 to 26.0) |
Anti-Mi-2 in DM (95% CI) | NA | 59%f (43.2 to 73.0) | NA | 15%f (3.2 to 37.9) | NA |
Anti-synthetase in PM/DM | 4% | 6% | 0% | 0% | 20% |
| 10.5 to 12.5 | 10.5 to 12.5 | 6.5 to 8.5 |
Genetic admixture estimate [ 29, 30] | | | | | |
African | 4% | 5% | 8% |
European | 46% | 67% | 61% |
Amerindian | 50% | 28% | 31% |