In the May issue of JACI, Guttman-Yassky et al. (J Allergy Clin Immunol 2011;127:1110-1118), in part 1 of a 2-part review, covered the clinical and pathological similarities and differences between psoriasis and atopic dermatitis (AD) with AD as the point of reference. They finish up in this month’s issue (J Allergy Clin Immunol 2011;127:1420-1432) with a broad discussion comparing the immune phenotypes and therapies for AD and psoriasis.
In part 1, Guttman-Yassky et al. pointed out that psoriasis and AD both present with defects in skin barrier function, skin lesions infiltrated by increased numbers of T cells and dendritic cells and upregulation of epidermal proliferation genes. They note that the chronic phase of AD is more similar to psoriasis than the acute phase. There are distinct differences though. AD patients are susceptible to bacterial and viral skin infections, which is not true for psoriasis patients. Also, AD skin is characterized by decreases in keratinocyte differentiation, cornification, moisture and lipid content. Though lipid depletion is also observed for psoriasis, it is characterized by increased differentiation and cornification. Cytokine milieu in AD is dominated by TH2 cells, while psoriasis is associated with TH1 and TH17 cytokines. Additionally, AD is associated with structural protein anomalies (e.g., filaggrin dysfunction) that are not observed in psoriasis.
The authors discuss in part 2 how the disorders were thought to be mediated by polarized T helper cell responses with TH2 dominance seen in AD; however, this simple dichotomy did not account for all observations, such as hyperkeratinization, seen in chronic AD. They point out that the discovery that TH17 and T22 cells affected epidermal activation eventually led to a new working model wherein psoriasis is mediated by TH1 and TH17 immunity, and AD is mediated by TH2 and T22 cell effects. Production of anti-microbial peptides (AMP) is known to be compromised in AD compared to psoriasis. This was originally attributed to the TH2 environment, but the authors comment that IL-17 deficiency as well as excessive TH2 cytokines can explain the decreased AMP production found in AD. Guttman-Yassky et al note that the impaired AMP production would explain increased susceptibility to skin infections in AD. In contrast, psoriasis is characterized by increased AMP production. The authors also discuss basic differences between AD and psoriasis with regard to differences in dendritic cell populations, AD-associated eosinophilia, barrier defects and inflammation, and mast cell production of interferon gamma (IFN-γ) in psoriasis.
Guttman-Yassky et al. finish up part II with a discussion of the prognosis and intervention for psoriasis and AD. Unlike AD, they note that active psoriasis can be completely resolved and treatment time is short. The authors comment that, in spite of their differences, both AD and psoriasis share epidermal hyperplasia, aberrant immunity, and skin barrier anomalies. This would suggest that immune-based strategies to correct barrier defects that have been developed for psoriasis might be effective for AD. Guttman-Yassky et al. detail current AD treatments and make a case for psoriasis therapies as intervention for AD.
Tell us what you think. Please feel free to post your own comments and/or predictions below.
Thursday, June 2, 2011
Chronic mucocutaneous candidiasis associated with impaired TH17 cell differentiation
In this month’s issue, Hanna and Etzoni (J Allergy Clin Immunol 2011;127:1433-1437) shed light on the primary players in the pathogenesis of chronic mucosal candidiasis (CMC). They review current knowledge of CMC as it is most commonly observed; namely, as secondary to other clinical conditions, particularly those that cause immunocompromise, such as HIV, diabetes mellitus, and T-cell deficiency disorders. Hanna and Etzoni then discuss CMC as a primary symptom in immunodeficiency disease, such as in hyper-IgE syndrome (HIES) and autoimmune polyendocrinopathy with candidiasis and ectodermal dysplasia (APECED), or, more rarely, with no other related clinical presentation.
The authors review the primary innate immune defense against Candida albicans, noting that activation of the Dectin-1 and -2 receptors mediate host response through spleen tyrosine kinase (Syk) and caspase recruitment domain member 9 (CARD9) to initiate T cell differentiation to produce multiple cytokines, particularly those associated with TH17 differentiation, IL-17 and IL-22. T regulatory cells are also mobilized and critical for containing the TH17 inflammatory response to C. albicans.
Hanna and Etzoni move on to discuss CMC as the primary clinical feature of HIES and point to research that has shown that a heterozygous mutation in the transcription factor, STAT3, is the cause of this syndrome. Impaired STAT3 signaling negatively impacts RORγt function, which is required for TH17 cell development. The authors point out that this is supported by clinical findings of very low circulating markers for TH17 cell lineage in patients with HIES.
They also review severe CMC as a major feature of the autoimmune disease, APECED. Unlike the transcription dysregulation in HIES, CMC in APECED results from high titers of neutralizing autoantibodies against IL-17 and IL-22. Finally, Hanna and Etzoni describe less common presentations of non-syndromic CMC, some of which are idiopathic, while others have autosomal inheritance associations. In the latter, the authors discuss a genetic analysis of familial CMC in 5 generations of an Iranian family, which revealed a loss-of-function mutation in CARD9.
The authors conclude noting that in most non-syndromic CMC cases the genetic defects are still unknown, though abnormal TH17 function or production was observed.
Tell us what you think. Please feel free to post your own comments and/or predictions below.
The authors review the primary innate immune defense against Candida albicans, noting that activation of the Dectin-1 and -2 receptors mediate host response through spleen tyrosine kinase (Syk) and caspase recruitment domain member 9 (CARD9) to initiate T cell differentiation to produce multiple cytokines, particularly those associated with TH17 differentiation, IL-17 and IL-22. T regulatory cells are also mobilized and critical for containing the TH17 inflammatory response to C. albicans.
Hanna and Etzoni move on to discuss CMC as the primary clinical feature of HIES and point to research that has shown that a heterozygous mutation in the transcription factor, STAT3, is the cause of this syndrome. Impaired STAT3 signaling negatively impacts RORγt function, which is required for TH17 cell development. The authors point out that this is supported by clinical findings of very low circulating markers for TH17 cell lineage in patients with HIES.
They also review severe CMC as a major feature of the autoimmune disease, APECED. Unlike the transcription dysregulation in HIES, CMC in APECED results from high titers of neutralizing autoantibodies against IL-17 and IL-22. Finally, Hanna and Etzoni describe less common presentations of non-syndromic CMC, some of which are idiopathic, while others have autosomal inheritance associations. In the latter, the authors discuss a genetic analysis of familial CMC in 5 generations of an Iranian family, which revealed a loss-of-function mutation in CARD9.
The authors conclude noting that in most non-syndromic CMC cases the genetic defects are still unknown, though abnormal TH17 function or production was observed.
Tell us what you think. Please feel free to post your own comments and/or predictions below.
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