Concept: Autoimmune diseases
Genetic diversity across different human populations can enhance understanding of the genetic basis of disease. We calculated the genetic risk of 102 diseases in 1,043 unrelated individuals across 51 populations of the Human Genome Diversity Panel. We found that genetic risk for type 2 diabetes and pancreatic cancer decreased as humans migrated toward East Asia. In addition, biliary liver cirrhosis, alopecia areata, bladder cancer, inflammatory bowel disease, membranous nephropathy, systemic lupus erythematosus, systemic sclerosis, ulcerative colitis, and vitiligo have undergone genetic risk differentiation. This analysis represents a large-scale attempt to characterize genetic risk differentiation in the context of migration. We anticipate that our findings will enable detailed analysis pertaining to the driving forces behind genetic risk differentiation.
Behcet’s disease is a multisystem autoimmune disease with variable clinial manifestations. The diagnosis may pose a difficult challenge for the clinician, who has to be familiar with the wide spectrum and combination of the symptoms of Behcet’s disease. It is considered a rare disease in Hungary, and there are only few reports on Behcet’s disease in the Hungarian literature. However, the past history of Hungary, the worldwide growing incidence of the disease, and the authors' experience raise the possibility that the occurrence of the disease is higher than previously thought. In this review the authors present and discuss literature data on the pathogenesis and pathomechanism, as well as their own experience concerning the symptomatology of Behcet’s disease in order to promote diagnosis and offer adequate therapy for the patients. The authors presume that the importance of the disease is underestimated in Hungary due to a considerable number of unrecognized cases and they propose to establish a national registry for Behcets disease. Orv. Hetil., 2013, 154, 93-101.
Alopecia areata (AA) is a common autoimmune disorder mostly presented as round patches of hair loss and subclassified into alopecia totalis/alopecia universalis (AT/AU) based on the area of alopecia. Although AA is relatively common, only 5% of AA patients progress to AT/AU, which affect the whole scalp and whole body respectively. To determine genetic determinants of this orphan disease, we undertook whole-exome sequencing of 6 samples from AU patients, and 26 variants in immune-related genes were selected as candidates. When an additional 14 AU samples were genotyped for these candidates, 6 of them remained at the level of significance in comparison with 155 Asian controls (p<1.92×10(-3)). Linkage disequilibrium was observed between some of the most significant SNPs, including rs41559420 of HLA-DRB5 (p<0.001, OR 44.57) and rs28362679 of BTNL2 (p<0.001, OR 30.21). While BTNL2 was reported as a general susceptibility gene of AA previously, HLA-DRB5 has not been implicated in AA. In addition, we found several genetic variants in novel genes (HLA-DMB, TLR1, and PMS2) and discovered an additional locus on HLA-A, a known susceptibility gene of AA. This study provides further evidence for the association of previously reported genes with AA and novel findings such as HLA-DRB5, which might represent a hidden culprit gene for AU.
Over the last few years, dermoscopy has been shown to be a useful tool in assisting the noninvasive diagnosis of various general dermatological disorders. In this article, we sought to provide an up-to-date practical overview on the use of dermoscopy in general dermatology by analysing the dermoscopic differential diagnosis of relatively common dermatological disorders grouped according to their clinical presentation, i.e. dermatoses presenting with erythematous-desquamative patches/plaques (plaque psoriasis, eczematous dermatitis, pityriasis rosea, mycosis fungoides and subacute cutaneous lupus erythematosus), papulosquamous/papulokeratotic dermatoses (lichen planus, pityriasis rosea, papulosquamous sarcoidosis, guttate psoriasis, pityriasis lichenoides chronica, classical pityriasis rubra pilaris, porokeratosis, lymphomatoid papulosis, papulosquamous chronic GVHD, parakeratosis variegata, Grover disease, Darier disease and BRAF-inhibitor-induced acantholytic dyskeratosis), facial inflammatory skin diseases (rosacea, seborrheic dermatitis, discoid lupus erythematosus, sarcoidosis, cutaneous leishmaniasis, lupus vulgaris, granuloma faciale and demodicidosis), acquired keratodermas (chronic hand eczema, palmar psoriasis, keratoderma due to mycosis fungoides, keratoderma resulting from pityriasis rubra pilaris, tinea manuum, palmar lichen planus and aquagenic palmar keratoderma), sclero-atrophic dermatoses (necrobiosis lipoidica, morphea and cutaneous lichen sclerosus), hypopigmented macular diseases (extragenital guttate lichen sclerosus, achromic pityriasis versicolor, guttate vitiligo, idiopathic guttate hypomelanosis, progressive macular hypomelanosis and postinflammatory hypopigmentations), hyperpigmented maculopapular diseases (pityriasis versicolor, lichen planus pigmentosus, Gougerot-Carteaud syndrome, Dowling-Degos disease, erythema ab igne, macular amyloidosis, lichen amyloidosus, friction melanosis, terra firma-forme dermatosis, urticaria pigmentosa and telangiectasia macularis eruptiva perstans), itchy papulonodular dermatoses (hypertrophic lichen planus, prurigo nodularis, nodular scabies and acquired perforating dermatosis), erythrodermas (due to psoriasis, atopic dermatitis, mycosis fungoides, pityriasis rubra pilaris and scabies), noninfectious balanitis (Zoon’s plasma cell balanitis, psoriatic balanitis, seborrheic dermatitis and non-specific balanitis) and erythroplasia of Queyrat, inflammatory cicatricial alopecias (scalp discoid lupus erythematosus, lichen planopilaris, frontal fibrosing alopecia and folliculitis decalvans), nonscarring alopecias (alopecia areata, trichotillomania, androgenetic alopecia and telogen effluvium) and scaling disorders of the scalp (tinea capitis, scalp psoriasis, seborrheic dermatitis and pityriasis amiantacea).
Acute transverse myelitis (ATM) is a severe complication of systemic lupus erythematosus (SLE). This study evaluated the clinical factors related to outcome in patients with SLE-associated ATM.
Atopic eczema (AE) is characterized by skin barrier and immune dysfunction. Null mutations in filaggrin (FLG), a key epidermal barrier protein, strongly predispose to AE; however, the precise role of FLG deficiency in AE pathogenesis remains incompletely understood.
B cells contribute to multiple aspects of autoimmune disorders and may play a role in triggering disease. Thus, targeting B cells may be a promising strategy for treating autoimmune disorders. Better understanding of the B cell subsets that are responsible for the development of autoimmunity will be critical for developing efficient therapies. Here we have reported that B cells expressing the transcription factor T-bet promote the rapid appearance of autoantibodies and germinal centers in spontaneous murine models of systemic lupus erythematosus (SLE). Conditional deletion of T-bet from B cells impaired the formation of germinal centers and mitigated the development of kidney damage and rapid mortality in SLE mice. B cell-specific deletion of T-bet was also associated with lower activation of both B cells and T cells. Taken together, our results suggest that targeting T-bet-expressing B cells may be a potential target for therapy for autoimmune diseases.
Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis is a severe condition encompassing two major syndromes: granulomatosis with polyangiitis (formerly known as Wegener’s granulomatosis) and microscopic polyangiitis. Its cause is unknown, and there is debate about whether it is a single disease entity and what role ANCA plays in its pathogenesis. We investigated its genetic basis.
Infection-triggered disease onset, chronic immune activation and autonomic dysregulation in CFS point to an autoimmune disease directed against neurotransmitter receptors. Autoantibodies against G-protein coupled receptors were shown to play a pathogenic role in several autoimmune diseases. Here, serum samples from a patient cohort from Berlin (n= 268) and from Bergen with pre- and post-treatment samples from 25 patients treated within the KTS-2 rituximab trial were analysed for IgG against human α and ß adrenergic, muscarinic (M) 1-5 acetylcholine, dopamine, serotonin, angiotensin, and endothelin receptors by ELISA and compared to a healthy control cohort (n=108). Antibodies against ß2, M3 and M4 receptors were significantly elevated in CFS patients compared to controls. In contrast, levels of antibodies against α adrenergic, dopamine, serotonin, angiotensin, and endothelin receptors were not different between patients and controls. A high correlation was found between levels of autoantibodies and elevated IgG1-3 subclasses, but not with IgG4. Further patients with high ß2 antibodies had significantly more frequently activated HLA-DR+ T cells and more frequently thyreoperoxidase and anti-nuclear antibodies. In patients receiving rituximab maintenance treatment achieving prolonged B-cell depletion, elevated ß2 and M4 receptor autoantibodies significantly declined in clinical responder, but not in non-responder. We provide evidence that 29.5% of patients with CFS had elevated antibodies against one or more M acetylcholine and ß adrenergic receptors which are potential biomarkers for response to B-cell depleting therapy. The association of autoantibodies with immune markers suggests that they activate B and T cells expressing ß adrenergic and M acetylcholine receptors. Dysregulation of acetylcholine and adrenergic signalling could also explain various clinical symptoms of CFS.
Celiac disease (CD) is an autoimmune disorder that occurs in genetically susceptible individuals of all ages and is triggered by immune response to gluten and related proteins. The disease is characterized by the presence of HLA-DQ2 and/or DQ8 haplotypes, diverse clinical manifestations, gluten-sensitive enteropathy and production of several autoantibodies of which endomysial, tissue transglutaminase and deamidated gliadin peptide antibodies are considered specific. Although anti-reticulin antibodies (ARA) have historically been used in the evaluation of CD, these assays lack optimal sensitivities and specificities for routine diagnostic use. This review highlights the advances in CD-specific serologic testing and the rationale for eliminating ARA from CD evaluation consistent with recommendations for diagnosis.