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Frontiers in Immunology 2019Adipose mesenchymal stem cells (ASC) are considered minimally immunogenic. This is due to the low expression of human leukocyte antigens I (HLA-I), lack of HLA-II...
Adipose mesenchymal stem cells (ASC) are considered minimally immunogenic. This is due to the low expression of human leukocyte antigens I (HLA-I), lack of HLA-II expression and low expression of co-stimulatory molecules such as CD40 and CD80. The low rate of observed immunological rejection as well as the immunomodulatory qualities, position ASC as a promising cell-based therapy for the treatment of a variety of inflammatory indications. Yet, few studies have addressed relevant aspects of immunogenicity such as ASC donor-to-patient HLA histocompatibility or assessment of immune response triggered by ASC administration, particularly in the cases of presensitization. The present study aims to assess allo-immune responses in a cohort of Crohn's disease patients administered with allogeneic ASC (darvadstrocel formerly Cx601) for the treatment of complex perianal fistulas. We identified donor-specific antibodies (DSA) generation in a proportion of patients and observed that patients showing preexisting immunity were prone to generating DSA after allogeneic therapy. Noteworthy, naïve patients generating DSA at week 12 (W12) showed a significant reduction in DSA titer at week 52 (W52), whereas DSA titer was reduced in pre-sensitized patients only with no specificities against the donor administered. Remarkably, we did not observe any correlation of DSA generation with ASC therapeutic efficacy. complement-dependent cytotoxicity (CDC) studies have revealed limited cytotoxic levels based upon HLA-I expression and binding capacity even in pro-inflammatory conditions. We sought to identify CDC coping mechanisms contributing to the limited cytotoxic killing observed in ASC . We found that ASC express membrane-bound complement regulatory proteins (mCRPs) CD55, CD46, and CD59 at basal levels, with CD46 more actively expressed in pro-inflammatory conditions. We demonstrated that CD46 is a main driver of CDC signaling; its depletion significantly enhances sensitivity of ASC to CDC. In summary, despite relatively high clearance, DSA generation may represent a major challenge for allogeneic cell therapy management. Sensitization may be a significant concern when evaluating re-treatment or multi-donor trials. It is still unknown whether DSA generation could potentially be the consequence of donor-to-patient interaction and, therefore, subsequently link to efficacy or biological activity. Lastly, we propose that CDC modulators such as CD46 could be used to ultimately link CDC specificity with allogeneic cell therapy efficacy.
Topics: Adipose Tissue; Adult; Animals; Cells, Cultured; Cohort Studies; Complement Activation; Crohn Disease; Female; Fistula; Graft Rejection; HLA Antigens; Humans; Immunity, Humoral; Immunization; Isoantigens; Male; Membrane Cofactor Protein; Mesenchymal Stem Cell Transplantation; Mesenchymal Stem Cells; Perianal Glands; Postoperative Complications; Transplantation, Homologous
PubMed: 31258526
DOI: 10.3389/fimmu.2019.01244 -
BMJ Case Reports Apr 2019Gynaecological infections are frequent in women, particularly in young women during their reproductive time. Anatomophysiologically, Bartholin's gland is greatly...
Gynaecological infections are frequent in women, particularly in young women during their reproductive time. Anatomophysiologically, Bartholin's gland is greatly susceptible to infections and is characterised by an inherent polymicrobial population. In fact, gynaecological microbiota has a set of agents coming from the perianal region that colonise the vagina and, in particular, Bartholin's gland. Taking this into account, infections caused by agents that do not belong to the genital microbiota are less frequent. Here, we describe a case of a 23-year-old young woman with an abscess in Bartholin's gland caused by .
Topics: Abscess; Anti-Bacterial Agents; Bartholin's Glands; Diagnosis, Differential; Drainage; Female; Humans; Pneumococcal Infections; Streptococcus pneumoniae; Treatment Outcome; Vulvar Diseases; Young Adult
PubMed: 31023734
DOI: 10.1136/bcr-2018-228492 -
International Archives of Allergy and... 2019Recurrent severe bacterial and fungal infections are characteristic features of the rare genetic immunodeficiency disorder chronic granulomatous disease (CGD). The... (Review)
Review
Recurrent severe bacterial and fungal infections are characteristic features of the rare genetic immunodeficiency disorder chronic granulomatous disease (CGD). The disease usually manifests within the first years of life with an incidence of 1 in approximately 200,000 live births. The incidence is higher in Iran and Morocco where it reaches 1.5 per 100,000 live births. Mutations have been described in the 5 subunits of NADPH oxidase, mostly in gp91phox and p47phox, with fewer mutations reported in p67phox, p22phox, and p40phox. These mutations cause loss of superoxide production in phagocytic cells. CYBB, the gene encoding the large gp91phox subunit of the transmembrane component cytochrome b558 of the NADPH oxidase complex, is localized on the X-chromosome. Genetic defects in CYBB are responsible for the disease in the majority of male CGD patients. CGD is associated with the development of granulomatous reactions in the skin, lungs, bones, and lymph nodes, and chronic infections may be seen in the liver, gastrointestinal tract, brain, and eyes. There is usually a history of repeated infections, including inflammation of the lymph glands, skin infections, and pneumonia. There may also be a persistent runny nose, inflammation of the skin, and inflammation of the mucous membranes of the mouth. Gastrointestinal problems can also occur, including diarrhea, abdominal pain, and perianal abscesses. Infection of the bones, brain abscesses, obstruction of the genitourinary tract and/or gastrointestinal tract due to the formation of granulomatous tissue, and delayed growth are also symptomatic of CGD. The prevention of infectious complications in patients with CGD involves targeted prophylaxis against opportunistic microorganisms such as Staphylococcus aureus, Klebsiella spp., Salmonella spp. and Aspergillus spp. In this review, we provide an update on organ involvement and the association with specific isolated microorganisms in CGD patients.
Topics: Autoimmunity; Bacterial Infections; Child; Child, Preschool; Female; Granulomatous Disease, Chronic; Humans; Infant; Liver Abscess; Lung Diseases; Male; Mycoses; NADPH Oxidases; Skin Diseases
PubMed: 30904913
DOI: 10.1159/000496181 -
Skin Appendage Disorders Nov 2018Extramammary Paget disease is a rare, slow-growing intraepithelial neoplasm of the skin or its underlying appendages. It more commonly affects the apocrine glands of the...
Extramammary Paget disease is a rare, slow-growing intraepithelial neoplasm of the skin or its underlying appendages. It more commonly affects the apocrine glands of the axilla, vulva, perianal region, scrotum, and/or penis. It often presents as a well-demarcated, thickened, erythematous, or gray-white scaly plaque with indolent growth that may become ulcerated, crusted, papillomatous, or eczematous over time. Pruritus, pain, and burning sensations are common symptoms; however, they are not appreciated by all patients. Many patients are erroneously treated for eczema for months to years before a proper diagnosis is reached. Patients presenting with chronic genital or perineal dermatitis or skin lesions that have been unresponsive to topical therapy should be biopsied for definitive diagnosis.
PubMed: 30643783
DOI: 10.1159/000488723 -
In Vivo (Athens, Greece) 2018Neoplastic lesions of perianal glands account for approximately 10% of all skin cancer cases in dogs. They occur in many dog breeds, usually in male animals aged over 6...
BACKGROUND/AIM
Neoplastic lesions of perianal glands account for approximately 10% of all skin cancer cases in dogs. They occur in many dog breeds, usually in male animals aged over 6 years. Due to their hormone-dependency, tamoxifen can be used in antineoplastic treatment. The aim of the study was to measure epidermal growth factor (EGF) levels in the serum of dogs with perianal tumours after tamoxifen treatment and to use it as a prognostic factor for further treatment.
MATERIALS AND METHODS
The study was performed on 19 male dogs aged between 6 and 14 years, diagnosed with neoplastic hyperplasia in the perianal region. The control group comprised 10 healthy dogs brought in for routine castration. The research material comprised blood drawn from the animals and tumour specimens for histopathology. The study group received 1-month treatment with tamoxifen. Blood serum was then tested for 17-β oestradiol level, and for EGF level on the first day of the therapy and 6 months after treatment completion.
RESULTS
Hepatoid gland adenomas were diagnosed in 10 cases, and hepatoid gland epitheliomas in nine cases. Elevated 17-β oestradiol levels were observed in all dogs. On the first day of treatment with tamoxifen, the serum EGF levels in all study groups were higher than in the control group. At the 6-month follow-up, the EGF levels were significantly reduced in hepatoid gland adenoma cases compared to those taken on the first day of treatment of tamoxifen, while in animals with hepatoid gland epithelioma, it was greatly increased and was correlated with relapse.
CONCLUSION
Perianal gland tumours are characterised by EGF overexpression, which can be helpful in early-stage prognosis and treatment. An increase in EGF levels 6 months after tamoxifen therapy correlates with disease progression and may be a useful prognostic factor.
Topics: Adenoma; Anal Gland Neoplasms; Animals; Carcinoma; Dogs; Epidermal Growth Factor; Male; Tamoxifen
PubMed: 30150441
DOI: 10.21873/invivo.11361 -
BMJ Case Reports Jul 2018Hidradenoma papilliferum is an uncommon benign tumour that is located in the anogenital region of middle-aged women. They are usually only diagnosed after excision and...
Hidradenoma papilliferum is an uncommon benign tumour that is located in the anogenital region of middle-aged women. They are usually only diagnosed after excision and are thought to arise from anogenital mammary-like glands. We present the case of a young woman who noticed a slow growing perianal lump which caused minimal symptoms.
Topics: Adenoma, Sweat Gland; Adult; Anus Neoplasms; Colonoscopy; Female; Humans; Immunohistochemistry; Perineum; Sweat Gland Neoplasms; Treatment Outcome
PubMed: 30061121
DOI: 10.1136/bcr-2017-220354 -
Alimentary Pharmacology & Therapeutics May 2018Patient reported outcomes regarding perianal disease and faecal incontinence in the community-based inflammatory bowel disease population are poorly described.
BACKGROUND
Patient reported outcomes regarding perianal disease and faecal incontinence in the community-based inflammatory bowel disease population are poorly described.
AIMS
To determine the impacts of perianal disease and faecal incontinence on quality of life and employment in inflammatory bowel disease patients.
METHODS
For this cross-sectional study, a comprehensive survey was sent out to members of the Dutch National Crohn's and Colitis patient organisation. Validated questionnaires regarding faecal incontinence and active perianal disease were used to estimate its prevalence's. The effect on the quality of life (36-Item Short Form Survey) and on employment status (multivariate binary regression analysis) was assessed in this inflammatory bowel disease population.
RESULTS
A total number of 1092 returned questionnaires (58% responders) were used for analysis; 750 respondents (69%) were female; mean age was 47 years (IQR 35-59). In 621 patients (57%) Crohn's disease, in 422 (39%) ulcerative colitis and in 49 (4%) patients unclassifiable inflammatory bowel disease was self-reported. The 114 patients (10%) with a stoma were excluded for continence related analyses. Faecal incontinence was reported in 555 patients (57%), was comparable between the different inflammatory bowel disease diagnoses and affected all 36-Item Short Form Survey subscales adversely (incontinence vs continence: Physical functioning 75 vs 84, P < 0.0001; Limitations due to physical health 49 vs 63, P < 0.0001; Limitations due to emotional problems 49 vs 64, P < 0.0001; Energy/fatigue 47 vs 53, P < 0.0001; Emotional well-being 71 vs 74, P = 0.005; Social functioning 63 vs 73, P < 0.0001; Pain 66 vs 75, P < 0.0001; General health 41 vs 48, P < 0.0001). Active perianal disease was reported in 39% Crohn's disease, 16% ulcerative colitis (84% fissures) and 20% unclassifiable inflammatory bowel disease patients. Faecal incontinence was more common in patients with perianal disease (67% vs 53%, P = 0.003). When correcting for age, disease duration, inflammatory bowel disease-related surgery and faecal incontinence, active perianal disease was independently affecting employment (OR 0.67; 95% CI 0.50-0.91; P = 0.01).
CONCLUSIONS
Faecal incontinence and perianal disease are quality of life determining factors. Faecal incontinence needs more attention among clinicians, and development of new (drug) therapies needs to be focussed on perianal disease.
Topics: Adult; Animals; Anus Diseases; Cross-Sectional Studies; Employment; Fecal Incontinence; Female; Humans; Inflammatory Bowel Diseases; Male; Middle Aged; Netherlands; Perianal Glands; Prevalence; Quality of Life; Surveys and Questionnaires
PubMed: 29520808
DOI: 10.1111/apt.14599 -
Anatomical Record (Hoboken, N.J. : 2007) May 2018To better understand the cellular origins and differentiation of anal canal epithelial neoplasms, the immunohistochemical profiles of the anal canal epithelium in humans... (Comparative Study)
Comparative Study
To better understand the cellular origins and differentiation of anal canal epithelial neoplasms, the immunohistochemical profiles of the anal canal epithelium in humans and swine were evaluated. Formalin-fixed tissue sections were immunostained for mucin (MUC: MUC2, MUC5AC, MUC5B), desmoglein 3 (DGS3), p63, CDX2, SOX2, and α-smooth muscle actin (α-SMA). The anal transitional zone (ATZ) epithelium covered the anal sinus and consisted of a stratified epithelium with mucous cells interspersed within the surface lining. Anal glands opened into the anal sinus. Ducts and acini of intraepithelial or periepithelial mucous type were the main structures of human anal glands, whereas those of swine were compound tubuloacinar mixed glands. Distal to the ATZ epithelium, non-keratinized stratified squamous epithelium merged with the keratinized stratified squamous epithelium of the perianal skin. MUC5AC expression predominated over MUC5B expression in the ATZ epithelium, while MUC5B expression was higher in the anal glands. SOX2 was positive in the ATZ epithelium, anal glands, and squamous epithelium except in the perianal skin. In humans, DGS3 was expressed in the ATZ epithelium, anal gland ducts, and squamous epithelium. p63 was detected in the ATZ epithelium, anal glands, and squamous epithelium. Myoepithelial cells positive for α-SMA and p63 were present in the anal glands of swine. Colorectal columnar cells were MUC5B /MUC2 /CDX2 /MUC5AC /SOX2 . The ATZ epithelium seems to be a distinctive epithelium, with morphological and functional features allowing smooth defecation. The MUC5AC /SOX2 /MUC2 /CDX2 profile of the ATZ epithelium and anal glands is a useful feature for diagnosing adenocarcinoma arising from these regions. Anat Rec, 301:796-805, 2018. © 2017 Wiley Periodicals, Inc.
Topics: Actins; Anal Canal; Animals; CDX2 Transcription Factor; Desmoglein 3; Epithelial Cells; Humans; Immunohistochemistry; Intestinal Mucosa; Mucins; SOXB1 Transcription Factors; Swine
PubMed: 29232767
DOI: 10.1002/ar.23748 -
Journal of Clinical Neuroscience :... Nov 2017Extramammary Paget disease is an intraepithelial neoplasm affecting cells rich in apocrine glands-often located in the vulvar, scrotal, or perianal region. It typically...
Extramammary Paget disease is an intraepithelial neoplasm affecting cells rich in apocrine glands-often located in the vulvar, scrotal, or perianal region. It typically affects older patients, between the ages of 50 and 80years old, and is most often limited to the epidermis. A 47-year-old Asian male first presented with enlargement of the right inguinal lymph node. A subsequent biopsy revealed extrammamary Paget disease of the scrotum. The patient eventually developed significant worsening back pain with bilateral lower extremity numbness and weakness three months later. Imaging demonstrated a pathologic compression fracture of the L4 vertebral body with metastatic epidural spinal cord compression. The patient underwent surgical decompression of the spine with bilateral L4 laminectomy, resection of epidural tumor, and pedicle screw fixation from L2 to S1. Surgical pathology demonstrated metastatic adenocarcinoma consistent with extramammary Paget disease. Although two other case reports have described spinal metastases from extramammary Paget disease, to the author's knowledge, this represents the first report of surgical decompression and fusion for extramammary Paget disease of the spine.
Topics: Adenocarcinoma; Decompression, Surgical; Epidural Neoplasms; Epidural Space; Fractures, Compression; Humans; Laminectomy; Male; Middle Aged; Paget Disease, Extramammary; Scrotum; Spinal Fractures
PubMed: 28887080
DOI: 10.1016/j.jocn.2017.08.018 -
The Indian Journal of Surgery Aug 2017Extramammary Paget's disease (EMPD) is uncommon and only a few cases have been reported in the literature. They are identical to the Mammary Paget's disease. This can...
Extramammary Paget's disease (EMPD) is uncommon and only a few cases have been reported in the literature. They are identical to the Mammary Paget's disease. This can occur where the apocrine glands are in abundance, more commonly in the genitalia and perianal area. We report here a case of Extramammary Paget's disease in the perianal region. The colourful background of this ulcer is analysed and the literature reviewed.
PubMed: 28827914
DOI: 10.1007/s12262-017-1590-6