Molecular and pathogenic effects of endoplasmic reticulum aminopeptidases ERAP1 and ERAP2 in MHC-I-associated inflammatory disorders: Towards a unifying view

The inflammatory diseases that are most strongly associated with major histocompatibility Complex class I (MHC-I) alleles are also influenced by endoplasmic reticulum aminopeptidase (ERAP) 1 and/or 2, often in epistasis with the susceptibility MHC-I allele. This review will focus on the four major MHC-I-associated inflammatory disorders: ankylosing spondylitis, birdshot chorioretinopathy, Behçet’s disease and psoriasis. The genetics of ERAP1/ERAP2 association and the alterations induced by polymorphism of these enzymes on the risk MHC-I allotypes will be examined. A pattern emerges of analogous effects on peptide length, sequence and affinity of disparate peptidomes, suggesting that similar peptide-mediated mechanisms underlie the pathogenesis and the joint contribution of ERAP1/ERAP2 and MHC-I to distinct inflammatory diseases. Processing of specific antigens, peptide-dependent changes in global properties of the MHC-I molecules, such as folding and stability, or both may be pathogenic.     

Common Exposure to STL Polyomavirus During Childhood

STL polyomavirus (STLPyV) was recently identified in human specimens. To determine seropositivity for STLPyV, we developed an ELISA and screened patient samples from 2 US cities (Denver, Colorado [500]; St. Louis, Missouri [419]). Overall seropositivity was 68%–70%. The age-stratified data suggest that STLPyV infection is widespread and commonly acquired during childhood.     

Case for diagnosis

Pemphigoid gestationis is a rare, autoimmune blistering dermatosis of pregnancy. No increase in fetal or maternal mortality has been demonstrated, but a greater prevalence of premature and small-for-gestationalage babies has been reported. Topical and systemic corticosteroids and antihistamines are the manstay of treatment. The authors report a case of a 27-year-old woman at 28-weeks gestation with sudden onset of pruriginous vesicles and blisters in the abdomen and limbs. Systemic corticosteroids were introduced and maintained throughout gestation to prevent flares and tapered after the birth of a healthy child.     

Peripheral ulcerative keratitis: Our challenging experience

A 52 year old male presented with peripheral ulcerative keratitis in the right eye. Patient’s history included retinitis pigmentosa, pseudophakia (right eye), cataract (left eye), bilateral partial deafness, ischemic heart disease, hypertension, type 1 diabetes mellitus, depression, hyperparathyroidism, hypertriglycemia and renal failure. The patient was on weekly hemodialysis. The peripheral corneal ulceration remained stable until he developed sudden and rapid thinning after eight months of regular follow up and management.Laboratory investigations including immunological studies were negative and we had to rely on treatment based on clinical signs, including the visual acuity, size, depth and staining of the ulcer and perilimbal, episcleral, scleral, corneal and anterior chamber reactions. The patient was treated with medical and conservative approaches and the eye was protected with a plastic shield to avoid injury. Despite our efforts, the patient perforated his eye due to a trivial trauma during sleep. He was managed successfully with cyanoacrylate glue and a bandage contact lens. The anterior chamber reformed after the perforation was sealed and the patient is on a regular follow up with a multidisciplinary approach.