Summary
Background
Pemphigus is a group of rare life‐threatening mucocutaneous autoimmune diseases, presenting mainly as two subtypes: pemphigus vulgaris (PV) and pemphigus foliaceus (PF). Inherited ...predispositions to pemphigus have long been speculated but they remain poorly understood.
Objectives
To identify common and specific nongenetic and genetic factors associated with pemphigus and its subtypes in the Chinese population.
Methods
A genome‐wide association study (GWAS) was performed in 496 unrelated patients with pemphigus (including 365 with PV and 104 with PF) and 1105 controls without pemphigus.
Results
A sex preference was observed only in PV (57·5% female) and not in PF (47·1% female). For male patients only, the mean age at diagnosis was significantly lower for PV than for PF (P < 0·001). The strongest associated single‐nucleotide polymorphisms are in the human leucocyte antigen (HLA) region: rs70993900 (PV; P = 1·5 × 10−45) and rs9469220 (PF; P = 1·1 × 10−8). HLA‐DQB1*05:03 ranks at the top (P = 4·7 × 10−40; odds ratio 12·4) in both subtypes, with significantly different risk allele frequency (RAFPV = 34·2% vs. RAFPF = 18·8% vs. RAFcontrol = 4·4%), whereas HLA‐DRB1*14:01 and HLA‐DRB1*04:06 are PV specific. HLA‐DQB1*03:03 and HLA‐DQB1*03:02 show significant subtype specificity in opposite directions. All of these associations were validated in the replication series with 147 cases of pemphigus and 604 controls. Multiple novel non‐HLA susceptibility loci were also identified in the GWAS.
Conclusions
This study represents the largest GWAS on pemphigus in the Chinese population published to date, and has allowed us to identify HLA haplotypes significantly shared between or specific to the two main subtypes of pemphigus.
What's already known about this topic?
Pemphigus is a group of autoimmune mucocutaneous diseases.
It has multiple subtypes associated with certain human leucocyte antigen (HLA) haplotypes in an ethnicity‐specific manner.
What does this study add?
This is the largest genome‐wide association study published on pemphigus to date.
We identified, for the first time, more than 100 single‐nucleotide polymorphisms (SNPs; six independent) at the HLA locus, with associations reaching genome‐wide significance.
Some of these SNPs are strongly associated with specific subtypes of pemphigus.
What is the translational message?
The identified new haplotypes can potentially serve as genetic markers to improve investigation of the epidemiology and pathogenesis of pemphigus and its specific subtypes.
Linked Comment: Geller. Br J Dermatol 2019; 180:713–714.
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Abstract Association of venous thromboembolic events (TEs) with malignancy is well known. Ewing's sarcoma usually presents as swelling at the primary site, however presenting as unilateral lower limb ...edema due to tumoral thrombosis of right iliac vein and IVC is a rare event. A 30-year-old male patient with extensive right lower limb swelling was admitted and imaging studies (plain film, ultrasonography, Doppler, computed tomography) revealed a mass arising from right iliac bone, adjoining sacrum and tumoral thrombosis of right iliac veins extending into inferior vena cava. Histopathological diagnosis was Ewing's sarcoma. Patient was treated successfully with chemotherapy and surgical embolectomy. So a young patient presenting with deep vein thrombosis should be investigated not only to establish any thrombophilic pre-disposition, but also let the clinician to suspect for any local malignancy. Treatment depends upon the proximal extent of tumoral thrombus. With advances in imaging and chemotherapeutic regimens early diagnosis is possible and appropriate treatment planning improves the prognosis. To our knowledge skeletal Ewing's sarcoma with bland thrombosis is a known entity however no such case with direct invasion of tumor into veins leading to tumoral venous thrombosis has been reported in medical literature.
