John Libbey Eurotext

European Journal of Dermatology

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Autoimmune bullous dermatoses: should we treat the patient or the antibodies? A preliminary study Volume 32, numéro 2, March-April 2022

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Serological detection of autoantibodies via indirect immunofluorescence (IIF) and enzyme-linked immunosorbent assays (ELISA) is usually helpful in the diagnostic process of autoimmune bullous dermatoses (AIBDs) [1]. ELISA provides objective and quantitative results, which may better reflect disease activity than those of IIF [1]. In fact, the titre of antibodies is reported to correlate with disease activity over time, especially anti-desmoglein (anti-Dsg) -1 and -3 in patients with pemphigus vulgaris (PV) and anti-BP180 in patients with bullous pemphigoid (BP). In contrast, the association between anti-BP230 titre and clinical course appears to be less evident [1, 2]. However, the association between titres of antibodies and disease activity and severity is still debated [3]. Should antibody titres guide therapeutic decisions or should they be based on clinical activity?

All patients who were diagnosed with BP or PV (histologically and/or based on laboratory findings) over a 12-month period were consecutively enrolled. They were evaluated clinically and their blood was collected for serology at T0, three months later (T1) and six months later (T2).

Clinical disease activity was given a score ranging 0-3. Patients with PV were given a score of 1 for moderate disease (Autoimmune Bullous Skin Disorder Intensity Score [ABSIS]<6.4), 2 for significant disease (6.4<ABSIS<31.5), and 3 for extensive disease (ABSIS>31.5) [4]. ABSIS was used rather than PDAI (Pemphigus Disease Area Index) because the latter has been validated as a score for PV with only 2 degrees of clinical severity [4]. Patients with BP were given a score of 1 for mild disease (Bullous Pemphigoid Disease Area Index [BPDAI]<20), 2 for moderate disease (20<BPDAI<57), and 3 for severe disease (BPDAI>57) [5]. When patients were free of mucocutaneous lesions, a score of 0 was given. IIF was performed to detect anti-skin antibodies in patients’ serum on monkey oesophagus substrate (BioSystems, Barcelona, Spain). The Mesacup-2 test desmoglein kit (Medical e Biological Laboratories, Nagoya, Giappone) was used for ELISA testing.

Clinical follow-up was continued for three years and relapses were recorded.

Thirty-six patients (26 with PV, 10 with BP) were evaluated at three timepoints (T0, T1 and T2). Clinical disease activity scores and laboratory results over time are reported in table 1.

Our results demonstrated a significant correlation between autoantibody titre and clinical activity for AIBDs, particularly PV, as both anti-Dsg-1 (p<0.0001) and anti-Dsg-3 titres (p=0.0004) reflected the clinical course of the disease. Moreover, the variation in autoantibodies titres between T0 and T2 correlated with variation in clinical activity scores (pp=0.0231 for anti-Dsg-3). Moreover, IIF positivity was associated with higher clinical activity for PV (p<0.0001).

In patients with BP, we found that titres of anti-BP180 significantly reflected clinical activity scores (p<0.0001), however correlation between T0 and T2 was not significant (p=0.3658). Titre of anti-BP230, as well as IIF positivity, did not correlate with clinical course (p = 0.8353 and p=0.8009, respectively).

Furthermore, considering patients with disease activity of 0 at T2, subsequent clinical relapses were not linked to higher antibody titres. Namely, 5/8 PV patients and 2/3 BP patients who relapsed during three years of follow-up had negative antibodies at T2.

Overall, our results for both PV and BP reflect those of the available literature, endorsing once more the use of ELISA and IIF as useful tools during follow-up of patients with AIBDs. For PV, titres of anti-Dsg-1 and anti-Dsg-3, as well as their variation with time, and IIF positivity were all reliable indices of disease activity. For BP, titre of anti-BP180 reflected clinical activity; therefore, we consider it useful in monitoring disease activity during follow-up. Conversely, IIF positivity, titre of anti-BP-230 and variation of titres with time did not parallel disease activity.

An interesting novelty is that, in our small sample, when remission is achieved, antibody titre cannot be considered a predictor of relapse of AIBD. Therefore, considerations for therapy should not rely on this titre. Surely, these findings need to be confirmed in larger, multicentric studies. We are also continuing clinical and serological follow-up for these patients.

To answer our initial question: although some serological markers may overlap with disease activity, in our opinion, the clinical picture should guide our therapeutic decisions.

Disclosures

Funding: none.

Conflicts of interest: none.