“…[18,25,26] Only three cases of PF are yet to be reported. [27][28][29] It is postulated to be due to the different distribution of Dsg 1 and 3 in neonate and adult skin and mucosae. [30] Most neonates had skin rather than mucosal lesions.…”
Pemphigus may be exacerbated during or after pregnancy, but often to a mild degree. Although the rate of stillbirth was not as high as previously reported, the rate of abortion was considerable. Pregnancy may have an uneventful course, especially in patients in clinical remission; nevertheless, careful monitoring of the high risk mother and fetus is mandatory.
“…[18,25,26] Only three cases of PF are yet to be reported. [27][28][29] It is postulated to be due to the different distribution of Dsg 1 and 3 in neonate and adult skin and mucosae. [30] Most neonates had skin rather than mucosal lesions.…”
Pemphigus may be exacerbated during or after pregnancy, but often to a mild degree. Although the rate of stillbirth was not as high as previously reported, the rate of abortion was considerable. Pregnancy may have an uneventful course, especially in patients in clinical remission; nevertheless, careful monitoring of the high risk mother and fetus is mandatory.
“…Alternatively, it is hypothesized that IgG4 anti-Dsg1 autoantibodies from the mother are retained by the placenta, which would act like an “immunoadsorbent” for pathogenic autoantibodies given that the placenta expresses desmosomes and desmogleins [11,12]. However, neonatal disease has been seen in PF indicating that there is sufficient passage of anti-Dsg1 IgG4 antibodies in these cases and presence of the target antigen in neonatal skin necessary to produce disease [16,17]. Differences in the intrinsic physical properties of the autoantibodies in FS such as affinity, avidity, or conformation, could also lead to different pathogenic potential for the IgG4 subclass.…”
Objectives
Fogo Selvagem (FS) in Limao Verde (LV), Brazil shows clinical and histological features of pemphigus foliaceus (PF) and shares pathogenic IgG4 anti-desmoglein 1 (Dsg1) autoantibodies. Previously, our group reported that mothers with active FS deliver babies with normal skin and low/negative titers of IgG4 autoantibodies by indirect immunofluorescence. It was postulated that maternal pathogenic IgG4 autoantibodies do not cross the placenta due to differential receptor mediated transplacental passage of IgG subclasses. It was also thought that placental Dsg1 may immunoadsorb pathogenic autoantibodies from the mother; hence pathogenic IgG4 autoantibodies do not reach the baby.
In this study we use a Dsg1-specific ELISA to test anti-Dsg1 autoantibodies of the IgM, IgG and the IgG subclasses in the sera of 68 pairs of normal mothers and their neonates living in a highly endemic area of FS. Determination of these baseline anti-Dsg1 autoantibodies will allow us to follow and predict in this and other cohorts the appearance of preclinical serological markers of FS.
Methods
The sera of mothers and neonates living in the endemic region were tested by ELISA for IgM, IgG and IgG subclasses using recombinant Dsg1 and anti-IgG subclass-specific monoclonal antibodies.
Results
The index values of anti-Dsg1 IgG1, IgG2 and IgG3 are similar in mothers and neonates (all p>0.18), while the index values of IgM, total IgG and IgG4 are higher in mothers (all p<0.001).
Conclusions
Narrowing the IgM, IgG and IgG subclasses of mothers and neonates to autoantibodies against Dsg1, we found, as expected, that IgM remains only in maternal circulation. In three mothers and two neonates we detected IgG4 anti-Dsg1 autoantibodies above the normal range. The remaining IgG subclasses show low values. The results of the neonatal sera will serve as a baseline for ongoing seroepidemiological studies of children and adults in the endemic regions of FS.
“…In a similar fashion, human maternal pemphigus autoantibodies transferred into the foetus through placental circulation induces neonatal pemphigus [6]. Pemphigus autoantibodies specifically induce blister formation, and anti-idiotype antibodies can neutralise the blistering induced by the injection of pemphigus IgG into Balb/c neonatal mice [7].…”
Apoptosis plays a role in pemphigus IgG-dependent acantholysis; theoretically, the blockade of the caspase pathway could prevent the blistering that is caused by pemphigus autoantibodies. Using this strategy, we attempted to block the pathogenic effect of pemphigus IgG in Balb/c mice by using the caspase inhibitor Ac-DEVD-CMK. This inhibitor was administrated before the injection of pemphigus IgG into neonatal mice. The main results of the present investigation are as follows: (1) pemphigus IgG induces intraepidermal blisters in Balb/c neonatal mice; (2) keratinocytes around the blister and acantholytic cells undergo apoptosis; (3) the caspases inhibitor Ac-DEVD-CMK prevents apoptosis; (4) the inhibition of the caspase pathway prevents blister formation. In conclusion, inhibition of the caspase pathway may be a promising therapeutic tool that can help in the treatment of pemphigus flare ups.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.