Bimodal immune activation in psoriasis Christophers, E.; Metzler, G.; Röcken, M.
British journal of dermatology (1951),
01/2014, Letnik:
170, Številka:
1
Journal Article
Recenzirano
Summary
Psoriasis is an immune‐regulated skin disease with various clinical subtypes and disease activities. The majority of patients present with predominantly stable plaques. At the onset of new ...lesions, plaque‐type psoriasis frequently demonstrates pin‐sized and highly inflammatory papules sometimes with an inflammatory border. The histopathology of initial psoriasis differs from stable plaque‐type psoriasis. Early lesions demonstrate innate immune cells with neutrophils, degranulating mast cells and macrophages. These are followed by interleukin (IL)‐1‐dependent T helper (Th)17 cells, finally resulting in the Th1‐dominated immunopathology of stable plaque‐type psoriasis, where mononuclear cells predominate with interspersed neutrophilic (Munro) microabscesses. These features suggest a bimodal immune pathway where alternate activation of either innate (autoinflammatory) or adaptive (autoimmune) immunity predominates. Neutrophilic infiltrations appear during early psoriasis with Munro abscesses. They are time limited and occur periodically, clinically best seen in linear nail pitting. These features strongly suggest a critical role for an IL‐1–Th17‐dominated autoinflammation in the initiation of psoriasis, followed by a Th1‐dominated late‐phase reaction. The concept of bimodal immune activation helps to explain results from therapeutic interventions that are variable and previously only partly understood.
What's already known about this topic?
The understanding of psoriasis has greatly advanced over the past 20 years. It started by recognizing psoriasis as a T‐cell‐mediated disease caused by interferon‐producing T cells.
Important roles for interleukin (IL)‐1‐related molecules have been uncovered, and partially underlined by clinical studies.
Because of the importance of different mediators such as tumour necrosis factor (TNF) and IL‐1, and T helper (Th)1 and Th17 immunity, psoriasis is increasingly viewed as a plethora of different diseases.
What does this study add?
Joining insights from genetics and immunology with clinical and histological pictures of single psoriasis lesions, here we suggest that psoriasis is one disease complex that appears at different levels.
Psoriasis starts as an IL‐1–TNF‐mediated, neutrophil‐dominated inflammation that initiates a Th17/Th22‐dominated early T‐cell infiltrate that turns into a Th1‐dominated psoriasis plaque.
Such plaques are sustained periodically by IL‐1–TNF‐producing squirting papillae that steadily deliver new psoriasis foci inside the lesion.
Pustular diseases and keratinocyte–myeloid synergy Christophers, E.; Schröder, J. M.
Journal of the European Academy of Dermatology and Venereology,
August 2022, 2022-08-00, 20220801, Letnik:
36, Številka:
8
Journal Article
Recenzirano
Odprti dostop
Pustules are among the most common lesions produced in human skin. Infections by pathogens and drug‐induced reactions are frequent causes of pustule formation. In recent years immune‐mediated ...pustular diseases have drawn attention. It is proposed to classify pustular diseases according to the initiating events and sites: purely epidermal pustules, follicular pustules or pustules noted in autoinflammatory syndromes. The unifying pathology in all of the three categories is a microinvasion of activated neutrophils into epidermal or adnexal epithelia. Formation of pustules involves established IL‐17 / IL‐23, IL‐36 / IL‐36RN driven pathology, or IL‐1 /caspase‐activated autoinflammation. Pathophysiology demonstrates an intriguing synergy of keratinocytes with neutrophils. This is called keratinocyte–myeloid synergy (KMS). Non‐infectious pustules are formed by IFNα controlling the production of chemoattractants (IL‐8, LTB4) or induced by IL‐1‐regulated inflammasomes and caspase/ IFNβ‐induced chemotaxins. The presence of physical barriers, for example, cornified cell layers (str. corneum), is instrumental in establishing chemotactic gradients and blocking migrating neutrophils. In follicular KMS‐driven pustular disorders, in contrast to epidermal pustules, neutrophil‐mediated toxicity propagates lasting and expanding ulcerating diseases with increased levels of circulating immunoglobulin A (IgA). Complexed IgA is suggested to propagate ongoing pustular diseases. These are prerequisites essential for developing pustules in burdensome human skin diseases.
Summary
Background Psoriasis is a common disease affecting all age groups. In contrast to adult psoriasis, only few studies on the epidemiology of childhood psoriasis have been published.
Objectives ... Assessment of prevalence and comorbidities of juvenile psoriasis in Germany based on health insurance data.
Methods Data were collected from a database of about 1·3 million nonselected individuals from a German statutory health insurance organization which covers all geographical regions. Individuals with psoriasis were identified by ICD‐10 codes applied to all outpatient and inpatient visits. The present analysis consists of all patients who were enlisted throughout the year 2005. The diagnosis of psoriasis was registered whenever there was at least one documented patient contact using code L40.* and subcodes. Comorbidities were also evaluated by ICD‐10 diagnoses.
Results In total, 33 981 patients with the diagnosis of psoriasis were identified. The prevalence in 2005 was 2·5%. The total rate of psoriasis in children younger than 18 years was 0·71%. The prevalence rates increased in an approximately linear manner from 0·12% at the age of 1 year to 1·2% at the age of 18 years. The overall rate of comorbidity in subjects with psoriasis aged under 20 years was twice as high as in subjects without psoriasis. Juvenile psoriasis was associated with increased rates of hyperlipidaemia, obesity, hypertension, diabetes mellitus, rheumatoid arthritis and Crohn disease.
Conclusions Psoriasis is a common disease in children. Like in adults, it is associated with significant comorbidity. Increased attention should be paid to the early detection and treatment of patients affected.
Comorbidities in psoriasis Christophers, E
Journal of the European Academy of Dermatology and Venereology,
11/2006, Letnik:
20, Številka:
s2
Journal Article
Recenzirano
Odprti dostop
Psoriasis is a common inflammatory skin disease. Epidemiological data demonstrate an association with a number of distinct disorders of the joints (psoriatic arthritis), the intestine (Crohn's ...disease), and skin (pustular disorders), as well as increased risk of cardiovascular disease. Systemic risk factors include obesity, hypertension, dyslipidaemia and diabetes. There is evidence that chronic inflammation may be causative. For dermatologists it has become mandatory to closely monitor psoriasis patients for comorbidities. Early anti‐inflammatory treatment regimens may prove to be preventive.
Summary
Psoriasis is a heterogeneous disorder with many different phenotypes. Further, different forms may alter their morphology and course of disease in that, for instance, plaque‐type psoriasis ...may become pustular and vice versa. With advancing insight in immunopathology phenotype switching can now be explained by directional changes from T cell‐mediated pathology to an inflammatory neutrophilic pattern which is driven by innate signalling. Within this framework not a single ‘antigen’ but various causative agents play a key role.
Psoriasis may express as active severe disease or as mild stable disease. In particular, patients with active severe disease present systemic involvement, including comorbidities and increased values ...of parameters reflecting an active state of innate immunity. In contrast, patients with mild stable disease show a dominancy of acquired immunity. In this review article, we report the clinical aspects of disease manifestations of both active and quiescent psoriasis as well as the immunological aspects, as well as the impact on antimicrobial resistance. The activity of psoriasis is not captured in the present outcome measures for severity assessment. The present review suggests that incorporating disease activity may be important in the assessment of the efficacy of treatments.
Previous studies have narrowed the interval containing PSORS1, the psoriasis-susceptibility locus in the major histocompatibility complex (MHC), to an ∼300-kb region containing HLA-C and at least 10 ...other genes. In an effort to identify the PSORS1 gene, we cloned and completely sequenced this region from both chromosomes of five individuals. Two of the sequenced haplotypes were associated with psoriasis (risk), and the other eight were clearly unassociated (nonrisk). Comparison of sequence of the two risk haplotypes identified a 298-kb region of homology, extending from just telomeric of HLA-B to the HCG22 gene, which was flanked by clearly nonhomologous regions. Similar haplotypes cloned from unrelated individuals had nearly identical sequence. Combinatorial analysis of exonic variations in the known genes of the candidate interval revealed that HCG27, PSORS1C3, OTF3, TCF19, HCR, STG, and HCG22 bore no alleles unique to risk haplotypes among the 10 sequenced haplotypes. SPR1 and SEEK1 both had messenger RNA alleles specific to risk haplotypes, but only HLA-C and CDSN yielded protein alleles unique to risk. The risk alleles of HLA-C and CDSN (HLA-Cw6 and CDSN*TTC) were genotyped in 678 families with early-onset psoriasis; 620 of these families were also typed for 34 microsatellite markers spanning the PSORS1 interval. Recombinant haplotypes retaining HLA-Cw6 but lacking CDSN*TTC were significantly associated with psoriasis, whereas recombinants retaining CDSN*TTC but lacking HLA-Cw6 were not associated, despite good statistical power. By grouping recombinants with similar breakpoints, the most telomeric quarter of the 298-kb candidate interval could be excluded with high confidence. These results strongly suggest that HLA-Cw6 is the PSORS1 risk allele that confers susceptibility to early-onset psoriasis.
Summary
For nearly 200 years it has been appreciated that plaque psoriasis consists of a number of distinct clinical phenotypes. However, a reliable and simple stratification of clinical presentation ...of psoriasis is lacking. In the era of immunogenetic association studies and an advanced understanding of the pathomechanisms of psoriasis it is important that a classification of the disease according to phenotype is readily available. Such a classification would facilitate clinically relevant interpretation of investigational data. A meeting of the International Psoriasis Council produced a consensus on clinical phenotypes of psoriasis equally relevant to clinical practitioners and psoriasis researchers.
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