AIM: To study serological antibodies in Caucasians and Asians, in health and inflammatory bowel disease (IBD), in Australia and Hong Kong (HK).

METHODS: Anti-glycan antibodies [anti-chitobioside (ACCA), anti-laminaribioside (ALCA)], and anti-mannobioside (AMCA), anti-Saccharomyces cervisiae (gASCA); and atypical perinuclear anti-neutrophil cytoplasmic antibody (pANCA) were tested in IBD patients, their unaffected relatives, and healthy controls in Australia and HK (China). Antibody status (positive or negative) and titre was compared between subjects of different geography, ethnicity and disease state.

RESULTS: Ninety subjects were evaluated: 21 Crohn’s disease (CD), 32 ulcerative colitis (UC), 29 healthy controls, and 8 IBD patient relatives. Forty eight subjects were Australian (29 Caucasian and 19 ethnic Han Chinese) and 42 were from HK (all Han Chinese). Caucasian CD patients had a significantly higher antibody prevalence of gASCA (67% vs 3%, P < 0.001), ALCA (44% vs 6%, P = 0.005), and AMCA (67% vs 15%, P = 0.002), whereas HK CD patients had a higher prevalence of only AMCA (58% vs 25%, P = 0.035), when compared with UC and healthy subjects in both countries. Caucasian CD had significantly higher gASCA prevalence (67% vs 0%, P < 0.001) and titre (median 59 vs 9, P = 0.002) than HK CD patients. Prevalence and titres of ALCA, ACCA and AMCA did not differ between CD in the two countries. Presence of at least one antibody was higher in Caucasian than HK CD patients (100% vs 58%, P = 0.045). pANCA did not differ between countries or ethnicity.

CONCLUSION: Serologic CD responses differ between HK Asian and Australian Caucasian patients. Different genetic, environmental or disease pathogenic factors may account for these differences.

Crohn’s disease (CD) and ulcerative colitis (UC) are related to a mucosal immune response to antigenic stimulation from the gut microbiota on a background of genetic susceptibility[1]. Serological antibodies for inflammatory bowel disease (IBD) have a role as diagnostic markers for IBD and assist in disease stratification[2].

Glycans are carbohydrate surface components, which can be found on immune cells, erythrocytes, tissue matrices and microorganisms. They likely reflect the interaction between the immune system and glycosylated cell wall components of microbiota such as fungi, yeast, and bacteria[3]. Anti-Saccharomyces cerevisiae (gASCA) (IgA and IgG) antibodies are directed against the cell wall mannan of the yeast Saccharomyces that shares homology with intestinal bacteria[4]. gASCA (antibodies against covalently immobilized mannan)[5] have been found to be comparable to ‘‘conventional’’ ASCA[6]. Anti-laminaribioside carbohydrate IgG antibodies (ALCA), anti-chitobioside carbohydrate IgA antibodies (ACCA), anti-mannobioside carbohydrate IgG antibodies (AMCA) were first reported in 2006[5] and discovered using GlycoChip glycan array technology[7]. These antibodies may allow differentiation of IBD from health, define between IBD subtypes, and have been associated with a more complicated CD behaviour[2,5]. Atypical perinuclear anti-neutrophil cytoplasmic antibody (pANCA) is regarded as a marker of UC, as it has a higher prevalence in UC than in CD or healthy controls[8].

Until two decades ago IBD was rare in Asia[9], but recent population-based and referral centre cohorts[10,11] have shown a rising incidence and prevalence of IBD in Asia[12]. These temporal trends in disease incidence and prevalence may provide insights into possible etiologic factors, such as genetic vs environmental. As serologic antibodies may represent an interface between a patient’s genetic make-up and their environment, we hypothesised that evaluation of serologic responses in areas of increasing incidence may provide an insight into these complex interactions. Most data on serological antibodies are derived from North American or European cohorts. There are no publications of the prevalence of the anti-glycan antibodies in Asian cohorts, either in Asia or in Asians abroad.

This study aimed to provide an initial insight into the prevalence and magnitude of the anti-glycan antibodies, and pANCA in IBD, compared to control groups, in Han Chinese (referred to as Asian) and Caucasian subjects in Australia and in Han Chinese subjects in Hong Kong (China).

There are very few studies reporting the prevalence of antibodies to microbial antigens in non-Western countries and between different ethnicities. This is the first report investigating anti-glycan antibodies in an Asian cohort, and the first report investigating pANCA in an Asian cohort residing in a country outside of Asia.

The prevalence of anti-glycan antibody in Australian Caucasian CD patients was consistent with previous published Western CD cohorts[14], and were more prevalent than in all other subjects studied. The exception was ACCA which had a high prevalence in the healthy Australian Asian (33%) and Caucasian (20%) subjects, in contrast to a previously reported lower prevalence (0.5%-12%) in other healthy cohorts[2].

gASCA was not present in any HK Asian CD subjects studied. This is in contrast to Asian data showing a similar prevalence of ASCA in Japanese[15] and South Korean[16,17] CD patients to that of Caucasian CD cohorts. A low gASCA titre was present in HK subjects. Chinese patients in HK may not raise an antibody response to this antigen, or may do it only in low titre. Lawrence et al[18] directly compared a HK IBD cohort with an Australian Caucasian IBD cohort and found ASCA IgG detection was similar but IgA was lower in Chinese CD patients. This IgG detection may differ from the gASCA IgG we measured, although the two antibody measurements have been said to correlate well[6].

Differences in prevalence of the anti-glycan antibodies may reflect true pathogenic differences in different populations. However they may still be present in some populations in low titre; this may need to be taken into account in non-Caucasian ethnicities.

AMCA was prevalent in Asian IBD patients and healthy Asian subjects. This antibody has low specificity for differentiating IBD from health in an Asian population. Bernstein et al[19] demonstrated a similar lack of specificity in a Canadian study of Caucasian and First Nations cohorts. He found a relatively high prevalence of IBD associated antibodies (pANCA, ASCA, anti-OmpC, anti-I2, and anti-CBir-1) in all First Nations cohorts (including controls). They concluded that these antibodies are unlikely to be of pathogenic significance.

pANCA was less prevalent in Asian UC than Caucasian UC patients. The lack of significance may relate to the small number of subjects studied and the modest difference observed. These findings are consistent with Asian UC studies from Japan (35%)[20], South Korea (22%)[21], and HK (44%)[18]. The prevalence in our Caucasian UC cohort was consistent with other Western UC cohorts[2].

Our study included 8 first-degree relatives of IBD patients (all Asian from HK), six related to CD patients, and 2 to UC patients. The only 2 relatives with a positive anti-glycan antibody were related to a CD patient, and for both it was a positive AMCA. There have been no studies of antibodies in relatives of IBD patients in Asian cohorts, however several studies have shown ASCA is present in 20%-56% of Caucasian healthy relatives of patients with CD[22-28]. None of the 8 relatives had a positive pANCA. Early studies of Caucasians demonstrated pANCA presence in 15%-30% of first degree relatives of patients with UC[29,30], however this has not been replicated[31-36], or not been significant when comparing to healthy non-related controls[37].

This study has a number of limitations. Sample sizes were small; however these data provide a basis for larger confirmatory studies. Australian Caucasian CD patients had more severe disease than Hong Kong Asian CD patients which could be contributing to differences in antibodies[38], however, because of the small numbers, comparisons between antibodies and CD phenotype were not made, but should be considered in further studies. Our lack of Australian Asian CD subjects limited our ability to separately determine the effects of ethnicity and geography. A cross sectional study on serological antibodies may be limited by changes in antibody status over time, although it appears that seropositive/seronegative antibody status remains relatively stable over time for the individual antibodies ASCA[13,14,23,38-41], ALCA, ACCA and AMCA[14,38,42].

In conclusion serological antibodies associated with IBD appear to differ in their presence and titre between the West and Chinese IBD patients. Caution should therefore be exercised in attributing pathogenic importance or using them as prognostic markers in different ethnic and geographic patient populations[43-45].

We are grateful to partial support by the Leona M and Harry B Helmsley Charitable Trust (ID). MAK was supported by a Research Fellowship from the Australian National Health and Medical Research Council (NHMRC), and by the St Vincent’s Research Endowment Fund. LP was supported by an Australian Postgraduate Award Scholarship.