APRIL is an important factor controlling B-cell function and allowing the survival of antigen-specific B cells. APRIL has been well studied in many autoimmune diseases and was found to be elevated. Its level also correlates in some of them with both disease severity and autoantibody levels. Few studied its role in dermatological diseases. When APRIL was studied in patients with atopic dermatitis, contradictory results were obtained 28,29. The concentration of APRIL was measured in patients with alopecia areata and was not significantly elevated when compared with controls 30.
Serum BLyS was studied in newly diagnosed PV and bullous pemphigoid (BP) patients and was compared with normal healthy participants by Asashima et al. 31. They found significant elevations of serum BAFF levels in patients with BP, but not with PV. According to their results, the BLyS levels appeared to increase when the skin lesions were actively spreading in the early stage of BP but not in PV.
Although BLyS is important for B-cell homeostasis it acts at early stages of B-cell development while APRIL seem to act later in maintaining both antigen-specific B cells and long-lived plasma cells 12–15. APRIL is expected to play a role in autoimmune blistering diseases as B cells are not only the precursors of antibody-secreting cells, but also have a regulatory role in immune responses. So we decided to study APRIL in one of the severe cutaneous autoimmune blistering diseases.
PV is an example of an autoimmune blistering skin disease where B cells play a central role. In the current study, serum APRIL levels were significantly elevated in patients with new active PV than both controlled PV cases on treatment and normal healthy participants. This is the first study to demonstrate difference in serum APRIL level between new active and controlled PV patients that might indicate role of APRIL in early development of PV as well as disease activity. In spite of the higher serum APRIL level in controlled PV on treatment than the normal healthy control the difference was not significant. This could be partially explained by the few number of normal healthy controls in the present study. The difference in serum APRIL level between controlled PV patients and normal healthy controls, in spite of being insignificant, may implicate that the serum APRIL level might decrease with treatment but still remaining higher than in normal healthy participants. This suggests a possible role of APRIL in recurrence or reactivation of the disease upon stopping the treatment which needs to be confirmed by further follow-up studies on relapsed PV patients.
In the present study, there was no association observed between age or sex and serum APRIL level in both PV groups. This is expected as the APRIL level was not previously reported to differ between men and women or to show change with aging. Serum APRIL level did not correlate with the duration of the disease in each of groups A and B, yet this could be explained by the significant difference in disease duration between new active PV and controlled PV cases. The mean disease duration in active PV cases in the present study was very short as this group included only newly diagnosed cases and excluding relapsed cases, whereas the duration of the disease was significantly higher in controlled PV patients on treatment. Yet we expect that if the relapsed active PV patients were also included and not just newly diagnosed cases, the results would be different.
The contradiction between the results of the present study and the previous studies could be explained by the difference in the patient selection criteria and also by the difference in the number of PV cases. In the present study in the active PV patients group, we included only newly diagnosed untreated patients, but in previous studies the active PV group includes also relapsed cases of PV after discontinuation of the treatment that could affect the serum APRIL level which might be elevated during the early stage of the disease and may not return to the same high level with the relapse. Unfortunately, there is only few available data on APRIL in PV for comparison as most of the studies conducted concentrate more on BP.
From the present study, we could conclude that APRIL may play a role in the early initial active stage of PV development, and that active PV patients had significantly higher APRIL serum level than both controlled PV patients on treatment and normal healthy participants. APRIL could be considered as a potential marker of early initial attack of PV. Targeting the APRIL system may be a potential therapeutic goal in the management of PV.
Further longitudinal follow-up studies are required to detect the change in serum APRIL level in PV patients with treatment and correlate it with the change in the level of anti-Dsg antibodies and to detect whether the APRIL level will show further elevation with relapse of the disease or not. Comparative studies between a larger number of normal healthy controls and controlled PV patients are needed to show possible significant differences in serum APRIL level.
Further therapeutic trials are also needed to study the possible effectiveness of inhibiting APRIL pathway using atacicept on active PV patients and for detecting the change in serum APRIL level in them.
There are no conflicts of interest.
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