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Reumatismo Sep 2022Since COVID-19 vaccination started in December 2020, different side effects were reported. This case report describes the possibility of developing disseminated herpes...
Since COVID-19 vaccination started in December 2020, different side effects were reported. This case report describes the possibility of developing disseminated herpes simplex infection after COVID-19 vaccine in a patient with rheumatoid arthritis. In this case report, we describe a 63-year-old Iranian female. She was a known case of seronegative rheumatoid arthritis and presented with generalized papulo-pustular itchy and painful skin lesions which appeared about seven days after the second dose of Sinopharm BIBP COVID-19 vaccine (BIBP-CorV). A biopsy of the skin lesions revealed acantholysis, neutrophils, and enlarged keratinocytes with eosinophilic intra-nuclear inclusions. Findings were consistent with herpes simplex infection. She was successfully treated by acyclovir. Disseminated cutaneous herpes simplex infection may have been triggered by COVID-19 vaccination. Reactivation of herpes virus after COVID-19 vaccines was reported in both rheumatic patients and other individuals. Whether having an underlying autoimmune inflammatory disorder could be an additional risk factor is still unknown.
Topics: Arthritis, Rheumatoid; COVID-19; COVID-19 Vaccines; Female; Herpes Simplex; Humans; Iran; Middle Aged; Skin Diseases; Vaccination
PubMed: 36101991
DOI: 10.4081/reumatismo.2022.1489 -
The Journal of Investigative Dermatology Feb 2023Pemphigus vulgaris is a severe autoimmune blistering disease characterized by IgG autoantibodies (auto-abs) against the desmosomal adhesion molecules desmoglein (DSG) 3...
Pemphigus vulgaris is a severe autoimmune blistering disease characterized by IgG autoantibodies (auto-abs) against the desmosomal adhesion molecules desmoglein (DSG) 3 and DSG1. Underlying mechanisms leading to blister formation upon binding of DSG-specific IgG auto-abs are not fully understood. Numerous studies showed the pathogenicity of IgG auto-ab binding to the aminoterminal region 1 (EC1) of the DSG3 ectodomain. However, auto-abs in pemphigus vulgaris are polyclonal, including IgG against both aminoterminal- and membrane-proximal epitopes of the DSG3 ectodomain. In this study, the pathogenicity of a previously uncharacterized murine monoclonal IgG antibody, 2G4, directed against the membrane-proximal region (EC5) of the DSG3 ectodomain was characterized and tested in various specificity and functionality assays. The results clearly show that 2G4 is capable of inhibiting intercellular keratinocyte adhesion and of inducing cellular DSG3 redistribution by activation of the p38MAPK signal transduction pathway. In this study, we provide evidence that an IgG auto-abs directed against the membrane-proximal region EC5 of DSG3 induces acantholysis, the hallmark in pemphigus vulgaris. These findings challenge the current concept that IgG auto-abs targeting the NH-terminal portion of the DSG3 ectodomain are pathogenic only. Our study provides further aspects for a deeper understanding of desmosomal keratinocyte adhesion and improves our insight into the complex auto-ab‒induced blister formation in pemphigus vulgaris.
Topics: Animals; Humans; Mice; Pemphigus; Desmoglein 3; Blister; Keratinocytes; Autoantibodies; Antibodies, Monoclonal; Immunoglobulin G; Desmoglein 1
PubMed: 36089007
DOI: 10.1016/j.jid.2022.07.030 -
The Journal of Dermatology Feb 2023We report a mother and an adult son with Darier's disease. The mother, 76 years old and Japanese, had positivity for anti-desmoglein (Dsg)1 antibodies. She had...
We report a mother and an adult son with Darier's disease. The mother, 76 years old and Japanese, had positivity for anti-desmoglein (Dsg)1 antibodies. She had erythema with hyperkeratosis and seborrheic and interstitial blistering. A high level of anti-Dsg1 antibodies was detected in the serum. Histopathological examination showed acantholysis and direct immunofluorescence testing revealed intercellular IgG and C3 deposition of the epidermis. Although she was diagnosed as having pemphigus foliaceus, the skin lesions slightly improved with immunosuppressive therapy. Her son, 47 years old, had similar skin lesions on the seborrheic and interstitial parts, but the anti-Dsg1 antibodies were negative in his serum. Histopathological examination showed acantholysis and dyskeratotic cells. Although Hailey-Hailey disease was first suspected, no mutation in the ATP2C1 was detected in either patient. Trio-exome analysis including the father showed a heterozygous c.2027C>A transition on exon 14 of ATP2A2, causing a replacement at amino acid 676 (p.Ala676Asp) in the mother and son only. The two patients were then diagnosed as having Darier's disease. Exome analysis further showed that a novel heterozygous missense mutation of DSG1 was identified only in the affected mother. Anti-Dsg1 antibody-positive Darier's disease is reported here for the first time. Very rare coexistence of Darier's disease and anti-Dsg1 antibody-positivity might be associated with this novel heterozygous DSG1 mutation. Experimental evidence is required to validate this hypothesis.
Topics: Humans; Child; Adult; Female; Aged; Middle Aged; Darier Disease; Acantholysis; Mothers; Pemphigus; Pemphigus, Benign Familial; Calcium-Transporting ATPases
PubMed: 36074695
DOI: 10.1111/1346-8138.16568 -
JAAD Case Reports Oct 2022
PubMed: 36035746
DOI: 10.1016/j.jdcr.2022.08.017 -
Molecular Immunology Oct 2022Pemphigus vulgaris (PV) is a chronic inflammatory autoimmune blistering disease. Aberrant SOCS3/STAT pathway activation is associated with many autoimmune diseases. This...
OBJECTIVE
Pemphigus vulgaris (PV) is a chronic inflammatory autoimmune blistering disease. Aberrant SOCS3/STAT pathway activation is associated with many autoimmune diseases. This study explored the relationship between activation of the SOCS3/STAT pathway and abnormally increased proportions of Th1 and Th17 cells in the peripheral blood of PV patients as well as the effect of CD4 T cells with abnormal SOCS3/STAT pathway activation on acantholysis.
METHODS
In PV patients, the proportions of Th1 and Th17 cells in peripheral blood, the levels of IFN-γ and IL-17 in serum and the mRNA levels of SOCS3 and STAT1/3 in CD4 T cells were detected. Then, SOCS3-knockdown primary CD4 T cells were prepared, and cocultured with HaCaT cells. Finally, after SOCS3 knockdown and coculture, CD4 T cells were collected, and the proportions of Th1 and Th17 cells, the protein levels of STAT1/3 and p-STAT1/3, and the levels of IFN-γ and IL-17 were measured. After 2 days of coculture, HaCaT cells were collected, inflammatory factors mRNA expression and acantholysis were assessed.
RESULTS
In PV patients, the proportions of Th1 (P = 0.016) and Th17 (P = 0.045) cells and the levels of IFN-γ (P = 0.010) were significantly increased. SOCS3 mRNA in CD4 T cells was significantly decreased (P = 0.008), whereas STAT1 (P = 0.043) and STAT3 (P = 0.004) mRNA were significantly increased. After SOCS3 knockdown, the proportions of Th1 (P < 0.001) and Th17 (P = 0.006) cells, the levels of IFN-γ (P < 0.001) and IL-17 (P = 0.001), and the protein levels of p-STAT1 (P = 0.001) and p-STAT3 (P = 0.003) were significantly increased in the CD4 T-shSOCS3-1 group. In the coculture system, the proportions of Th1 (P < 0.001) and Th17 (P < 0.001) cells, the levels of IFN-γ (P < 0.001) and IL-17 (P < 0.001), and the number of cell fragments (P < 0.001) were significantly increased in the CD4 T-shSOCS3-1+HaCaT-PV-IgG group, whereas the protein level of desmoglein3 (Dsg3) was significantly decreased. In addition, PV-IgG significantly increased IFN-γ and IL-6 mRNA in HaCaT cells.
CONCLUSION
Low SOCS3 expression in CD4 T cells from PV patients leads to overactivation of STAT, which causes CD4 T cells to overdifferentiate into Th1 and Th17 cells. Additionally, PV-IgG-induced local inflammation in skin lesions, which is mediated by IFN-γ and IL-6, can aggravate this phenomenon. Furthermore, low SOCS3 expression in CD4 T cells further exacerbates PV-IgG-induced acantholysis. Therefore, upregulating the expression of SOCS3 in CD4 T cells of PV patients and maintaining the balance of the IFN-γ/STAT1/SOCS3 and IL-6/STAT3/SOCS3 pathways can alleviate acantholysis in patients with PV.
Topics: Acantholysis; CD4-Positive T-Lymphocytes; Cell Differentiation; Humans; Immunoglobulin G; Interleukin-17; Interleukin-6; Pemphigus; RNA, Messenger; Suppressor of Cytokine Signaling 3 Protein; Suppressor of Cytokine Signaling Proteins; Th1 Cells; Th17 Cells
PubMed: 36030709
DOI: 10.1016/j.molimm.2022.08.007 -
Frontiers in Immunology 2022Molecular mechanisms underlying auto-antibody-induced acantholysis in pemphigus vulgaris are subject of current research to date. To decipher the discrepancy between...
Molecular mechanisms underlying auto-antibody-induced acantholysis in pemphigus vulgaris are subject of current research to date. To decipher the discrepancy between ubiquitous antibody binding to the epidermal desmosomes, but discontinuous disease manifestation, we were able to identify Ultraviolet A (UVA) as a cofactor for acantholysis. UVA induces interleukin (IL)-1 secretion in keratinocytes, mirroring innate immune system activation. In an keratinocyte dissociation assay increased fragmentation was observed when UVA was added to anti-Desmoglein 3 Immunoglobulins (anti-Dsg3 IgG). These results were confirmed in skin explants where UVA enhanced anti-Dsg3-mediated loss of epidermal adhesion. The UVA-mediated effect was blocked by the pan-caspase-inhibitor zVAD-fmk. Thus, we introduce UVA as a caspase-dependent exogenous cofactor for acantholysis which suggests that local innate immune responses largely contribute to overt clinical blister formation upon autoantibody binding to epidermal cells in pemphigus vulgaris.
Topics: Acantholysis; Caspases; Humans; Immunity, Innate; Immunoglobulin G; Pemphigus
PubMed: 35928825
DOI: 10.3389/fimmu.2022.898819 -
Italian Journal of Dermatology and... Aug 2022
Topics: Acantholysis; Dermoscopy; Humans; Ichthyosis; Microscopy, Confocal; Nivolumab
PubMed: 35916188
DOI: 10.23736/S2784-8671.22.07180-8 -
Journal of Cosmetic Dermatology Nov 2022E-cadherin is a classic cadherin that mediates keratinocyte adhesion.
BACKGROUND
E-cadherin is a classic cadherin that mediates keratinocyte adhesion.
AIMS
To assess the tissue expression of E-cadherin and its proteolytic serum fragment (soluble E-cadherin) in pemphigus vulgaris (PV) before and after clinical remission compared with controls.
PATIENTS
Thirty-seven PV patients and thirty controls were enrolled. Pemphigus disease area index (PDAI) was calculated for patients at baseline and after remission. Punch biopsy specimens were taken from patients before, and after remission, and from controls for assessment of tissue E-cadherin by immunofluorescence. Similarly, serum samples were collected for assessment of serum soluble E-cadherin by ELISA.
RESULTS
Presence, intensity, and mean intensity of tissue E-cadherin were significantly reduced in PV patients before treatment compared with controls (p < 0.001). Detected E-cadherin showed mainly a basal and suprabasal distribution with cell surface and a cytoplasmic expression. Serum E-cadherin was significantly higher in patients before treatment compared with controls (p = 0.006). With remission, tissue E-cadherin presence, intensity, mean intensity, and serum E-cadherin showed statistically significant improvement (p = 0.003, <0.001, <0.001, and 0.003 respectively). Tissue E-cadherin presence and serum E-cadherin level reached values equivalent to the controls (p = 0.49 and 0.44, respectively).
CONCLUSIONS
Disruption of tissue E-cadherin and upregulation of serum soluble E-cadherin can contribute to the pathogenesis of PV. Clinical remission of PV is associated with normalization of tissue and serum E-cadherin.
Topics: Humans; Pemphigus; Case-Control Studies; Desmoglein 3; Skin; Keratinocytes
PubMed: 35912419
DOI: 10.1111/jocd.15284 -
Paraneoplastic Pemphigus Autoantibodies Against C-terminus of Desmoplakin Induced Acantholysis and .Frontiers in Immunology 2022Paraneoplastic pemphigus (PNP) is an autoimmune bullous disease associated with underlying neoplasms and characterized by antibodies against desmoglein 3 (Dsg 3) and...
Paraneoplastic pemphigus (PNP) is an autoimmune bullous disease associated with underlying neoplasms and characterized by antibodies against desmoglein 3 (Dsg 3) and plakins. Autoantibodies against desmoglein 3 in sera of patients with PNP have been proven to cause acantholysis in neonatal mice. As a member of the plakin family, autoantibodies against desmoplakin were detected frequently by immunoprecipitation in the sera of PNP. The recombinant C-terminus of desmoplakin was expressed and purified to adsorb the specific autoantibodies against the C-terminus of desmoplakin. dispase-dependent keratinocyte dissociation assay and IgG passive transfer into neonatal mice assay were performed, followed by the electronic microscopy examination and TUNEL assay. We found that anti-C terminus of desmoplakin autoantibodies caused blisters and acantholysis in mice skin at a dose-dependent manner. Moreover, dissociated fragments were observed after incubation with the purified IgG against desmoplakin, compared with normal human IgG (-value =0.0207). The electronic microscopy examination showed the disconnection of keratin intermediate filaments from desmosomes. Lastly, apoptosis of keratinocytes in the TUNEL assay was all detected in the skins of neonatal mice after injection of the anti-C terminus of desmoplakin autoantibodies. Taken together, the study suggests that autoantibodies against the C-terminus of desmoplakin might be pathogenic in PNP.
Topics: Acantholysis; Animals; Autoantibodies; Autoimmune Diseases; Desmoglein 3; Desmoplakins; Humans; Immunoglobulin G; Mice; Paraneoplastic Syndromes; Pemphigus
PubMed: 35911677
DOI: 10.3389/fimmu.2022.886226 -
Clinical, Cosmetic and Investigational... 2022Grover's disease (GD), also known as Transient acantholytic dermatosis, has no typical clinical rash features. It usually occurs in elderly white men but very rarely in...
Grover's disease (GD), also known as Transient acantholytic dermatosis, has no typical clinical rash features. It usually occurs in elderly white men but very rarely in China. This is a disease of acantholysis and dyskeratosis, which is usually considered to be spontaneous remission. The skin lesions of the disease are diverse, and the main symptom is severe itching. We have reported a case of GD in a 14-year-old Chinese Tibetan male whose clinical manifestations were pruritic red papule, generalized red papules, papulo vesicles and blisters ranging from millet rice to soybean size. Skin lesions change rapidly and variously. In order to confirm the diagnosis, we have done skin biopsies, immunofluorescence, dermoscopy, microscopy and other examinations. Pathological skin biopsy showed acantholysis. Intraepidermal blisters and the presence of blisters on the basal cells as well as under the stratum corneum can be observed on the same pathological section. Type IV collagen immunohistochemistry showed blisters in the epidermis. The diagnosis of GD depended on the exclusion of other diseases. After we performed whole exon sequencing (WES) on DNA from the patient's blood, pathogenic gene mutations were not found. Pustular psoriasis, Subcorneal pustular dermatosis, Herpesvirus infections, Dermatitis herpetiformis, Pemphigus vulgaris, Norwegian scabies, Darier's disease, and Hailey-Hailey disease were all excluded. We successfully treated adolescent GD with minocycline combined with methotrexate. The patient was followed up for 19 months without recurrence.
PubMed: 35874457
DOI: 10.2147/CCID.S373228