Summary
Background
Despite the established pathogenic role of anti‐desmoglein (Dsg) antibodies in classical pemphigus, the significance of autoantibodies to another desmosomal cadherin, desmocollin ...(Dsc) is at present unknown. No consistent immunoassay for immunoglobulin (Ig) G autoantibodies to Dscs has been developed.
Objectives
The aim of this study was to develop reliable assays to detect anti‐Dsc autoantibodies.
Methods
We expressed soluble recombinant proteins (RPs) of human Dsc1–3 in mammalian cells and examined sera of various types of pemphigus, including 79 paraneoplastic pemphigus (PNP) sera, by novel enzyme‐linked immunosorbent assays (ELISAs) using the RPs. We also performed ELISAs of Dsc baculoproteins and used the complementary DNA (cDNA) transfection method, and compared the results with those of mammalian ELISAs.
Results
Through mammalian ELISAs, IgG autoantibodies to Dsc1, Dsc2 and Dsc3 were detected in 16·5%, 36·7% and 59·5% of PNP sera, respectively, and considerable numbers of pemphigus herpetiformis (PH) and pemphigus vegetans (PVeg) sera reacted strongly with Dsc1 and Dsc3. Mammalian ELISAs were highly specific and more sensitive than baculoprotein ELISAs or the cDNA transfection method. Several Dsc‐positive sera, particularly PH sera, showed no reactivity with Dsgs. The reactivity of PNP serum and PVeg serum with Dscs was not abolished by pre‐absorption with Dsg RPs.
Conclusions
The results of these novel ELISAs indicated that IgG anti‐Dsc autoantibodies were frequently detected and potentially pathogenic in nonclassical pemphigus.
What's already known about this topic?
Despite the established pathogenic role of anti‐desmoglein (Dsg) antibodies in classical pemphigus, the significance of autoantibodies to another desmosomal cadherin, desmocollin (Dsc), is at present unknown.
No consistent immunoassay for IgG autoantibodies to Dscs has been developed.
What does this study add?
We have successfully established new sensitive and specific mammalian Dsc immunoglobulin (Ig) G enzyme‐linked immunosorbent assays.
Our data show that IgG anti‐Dsc autoantibodies are frequently detected and potentially pathogenic in particular types of nonclassical pemphigus.
Summary
We report a unique case of a Japanese woman with herpetiform pemphigus (HP) who had IgG autoantibodies reactive with nondesmosomal sites of keratinocytes and presented characteristic ...transmission electron microscopic (TEM) findings of various‐sized vacuoles in keratinocytes without acantholysis. The patient presented with pruritic annular oedematous erythemas with small blisters lining the margins on the trunk and extremities. Histopathological examinations showed intraepidermal blisters with prominent infiltrations of eosinophils. Direct and indirect immunofluorescence tests revealed the presence of in vivo bound and circulating IgG autoantibodies to the keratinocyte cell surfaces. However, enzyme‐linked immunosorbent assays for desmoglein (Dsg) 1, Dsg3 and desmocollins 1–3 showed negative results. Immunoblotting using the full‐length human Dsg1 recombinant protein showed a positive band. TEM examination showed various‐sized vacuoles squashing the nuclei in many keratinocytes, resulting in rupture of the cells. Immunoelectron microscopic examination revealed IgG deposition over the entire keratinocyte cell surfaces, which spared the desmosomes. IgG antibodies were also present on the inside walls of the vacuoles around the nuclei of keratinocytes and on the cell surfaces of infiltrating eosinophils. This patient also had marked eosinophilia and high levels of thymus and activation‐regulated chemokine and interleukin‐5 in the serum. These results indicated a novel autoantigen on the nondesmosomal keratinocyte cell surfaces and the pathogenesis of bullous spongiotic change with inflammation in HP.
What's already known about this topic?
Herpetiform pemphigus (HP) is a rare variant of pemphigus characterized clinically by pruritic annular erythemas with vesicles resembling dermatitis herpetiformis and histopathologically by eosinophilic spongiosis without apparent acantholysis.
The targets of IgG autoantibodies in patients with HP are usually desmoglein 1 and 3, which are both components of desmosomes.
What does this study add?
This study reports the unique case of a patient with HP with IgG autoantibodies reactive to nondesmosomal sites of keratinocytes and characteristic transmission electron microscopic findings of various‐sized vacuoles in keratinocytes, while desmosomal adhesion remained.
Regarding pathogenesis, we speculate that the ballooning vacuoles might result in the bullous spongiotic changes without acantholysis seen in this patient.
This study also focuses on the relationships between blood eosinophil counts, serum thymus and activation‐regulated chemokine levels and HP disease activity.
Linked Comment: Yuan and Pan. Br J Dermatol 2019; 180:22.
Abstract The purpose of this study was to examine the efficacy of ultrasonography (US) and unenhanced magnetic resonance imaging (MRI) to determine the location of the internal maxillary artery (IMA) ...before orthognathic surgery. The study subjects were 19 patients (seven males and twelve females) with mandibular prognathism seen at the authors’ institution between March 2012 and April 2013. The distance from the skin to the IMA (S-IMA) and the distance from the mandibular notch to the IMA (MN-IMA) were measured. Using the US and coronal MRI images, S-IMA(cl) and MN-IMA(cl) in the closed position and S-IMA(op) and MN-IMA(op) in the open position were measured at a total of four points in each cross-section. There were significant correlations between the distances measured on coronal MRI and US for all groups ( P < 0.05). A total of 35 (92%) IMAs were classified as clear and three (8%) as unclear based on the US findings. Regarding the location of the IMA, 37 of the 38 sides studied (97%) were of the lateral type, while only one (3%) was of the medial type. The results of this study indicate that US can be used effectively to determine the location of the IMA.
Abstract We investigated changes in the sensitivity of cutaneous points and the oral mucosa after sagittal split ramus osteotomy (SSRO) and assessed the differences between SSRO and intraoral ...vertical ramus osteotomy (IVRO). The subjects included in this study were 46 patients with mandibular prognathism who underwent IVRO (88 rami) and 30 patients who underwent SSRO (59 rami). An objective evaluation of the neurosensory status of each patient was completed preoperatively and at 1, 4, 8, 12, and 24 weeks postoperatively. Other variables studied for each patient included sex, age, magnitude of mandibular setback, and amount of blood loss during surgery. We found that a neurosensory recovery occurred earlier in the oral mucosa than at cutaneous points. The number of oral mucosa points showing reduced neurosensory function and neurosensory disturbance after SSRO was significantly higher than after IVRO at 1, 4, and 8 weeks ( P < 0.05). The nerve recovery observed after SSRO was delayed for a longer period than that noted in our previous study of IVRO. In conclusion, we found changes in sensitivity at cutaneous points and the oral mucosa after SSRO and assessed the differences between SSRO and IVRO.
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