## 4 Discussion
Indeed, closer follow-up schedules in patients with BP180 \(>\) 20 may potentially allow clinicians to treat relapses at early stages, shortening the interval for an additional increase in steroids and steroids-sparing agents to achieve disease control. At the same time, BP180 ELISA may help identify those patients with a reduced risk of relapse who may benefit from therapy withdrawal or a decrease in minimal therapy dosage. A correlation between circulating anti-BP180 and clinical severity is well established for cutaneous BP. [PERSON] et al. found that BP180 ELISA correlated with ABSIS in a cohort of 42 treatment-naive BP patients [15]. [PERSON] et al., in a recent review, focused on the factors associated with the activity and severity of bullous pemphigoid and also included IgG autoantibodies against the NC16A domain of BP180 as closely correlated with the activity and severity of BP [16]. Concerning OMMP patients, the present results are in agreement with [PERSON] et al., who found a linear correlation between BP180 NC16A ELISA and ODSS [8]. Of note, [PERSON] et al. investigated the same immunodominant region NC16A of BP180 but used a different commercially available kit (MBL, Nagoya, Japan) which, according to the manufacturer's recommendations, adopts a different cutoff value for BP180-NC16A (9.0 U/mL vs. 20 U/mL). Indeed, the rate of OMMP patients that authors found positive for BP180 NC16A ELISA was 50% (15/30), which is moderately greater than the rate of 34% (17/44) found in the present study using a cut-off of 20 U/mL. Despite the fact that the heterogeneity in the adopted cut-off may generate different diagnostic performances, the relationship between BP180 levels and ODSS was confirmed by independent laboratories using different commercial kits. This strengthens the findings of the present study and suggests that ELISA is a good technique to be investigated as a biomarker of clinical severity. Moreover, ELISA was reported to be superior to IIF on salt-split skin (SSS), another serological technique employed in the diagnosis of subepidermal autoimmune blistering diseases, which permits the differentiation of circulating antibodies targeting dermal antigens from those targeting subepidermal regions [17]. Other serological methods like immunoprecipitation and immunoblotting are highly sensitive but are non-quantitative and thus difficult to correlate with the severity of OMMP [18]. A major limitation of BP180-NC16A is that it recognizes only a single portion of BP180. However, [PERSON] et al. demonstrated that regions other than NC16A may be recognized by MMP autoantibodies, especially against the C-terminal portion of BP180 [19]. It would be interesting in the future to also investigate if the presence of IgG directed against other regions of BP180 may influence clinical severity in OMMP. [PERSON] et al. developed an experimental full-length BP180 ELISA, but commercially available ELISA kits for similar purposes are still lacking [20]. At the same time, since other antigens such as integrin \(\alpha\)6, \(\beta\)4, and laminin 332 have been reported to be targeted by MMP autoantibodies [3], and some of these targets are covered by commercially available ELISA Kits, future efforts should be made to disclose potential relations between circulating antibodies targeting \(\alpha\)6, \(\beta\)4 integrin, and/or laminin 332 and ODSS in OMMP. Only a few other studies have investigated the relationship between circulating IgG anti-BP180 and clinical severity in OMMP. [PERSON] et al. found that the combination of IgG and IgA against BP180 with immunoblotting was associated with a more severe phenotype [4]. In the present study, IgA deposits at DIF were negatively associated with ODSS, and the association was maintained in multivariate analysis. DIF is not able to discriminate the target antigen of IgA deposits. It is thus difficult to draw conclusions about the role of IgA and clinical severity in OMMP.