Transcriptome patterns in hidradenitis suppurativa: support for the role of antimicrobial peptides and interferon pathways in disease pathogenesis.

BACKGROUND: Hidradenitis suppurativa (HS) is a recurrent inflammatory disease of the apocrine sweat glands. Immune dysregulation probably contributes to the pathogenesis of HS. AIM: To harness mRNA expression arrays to investigate the transcriptome profile in HS compared with control skin. METHODS: Illumina® HumanHT-12 v4 Expression BeadChips were used to measure mRNA expression in skin samples from HS (n = 10) and abdominoplasty (n = 11) skin specimens. Differentially expressed genes were detected by fitting genewise linear models to the normalized expression data and then modelling using the web-based software Ingenuity® Pathway Analysis. RESULTS: The antimicrobial peptide Dermcidin and the cytokine regulator interleukin (IL)-37 were both significantly downregulated in the HS specimens (Dermcidin expression log ratio -3.93, expression P = 0.04; IL-37 expression log ratio -3.29, expression P < 0.001). Pathway analysis revealed the interferon-signalling pathway, leucocyte extravasation pathway, T helper 1 and 2 pathways and nuclear factor of activated T cells as the top-five upregulated pathways in the HS samples. CONCLUSION: Evaluation of transcriptome patterns in HS compared with normal skin demonstrated downregulation of the antimicrobial peptide Dermcidin and the innate immune regulator IL-37, as well as upregulation of interferon pathways and pathways of leucocyte activation.

A comparison of immunometric and radioimmunoassay measurement of ACTH for the differential diagnosis of Cushing's syndrome.

OBJECTIVE: Measurement of plasma ACTH levels by radioimmunoassay (RIA) is used to identify adrenal causes (AA) of Cushing's syndrome (CS) and to distinguish ectopic CS (EAS) from Cushing's disease (CD) using CRH stimulation testing and inferior petrosal sinus sampling (IPSS). We wished to determine whether diagnostic criteria developed with RIA would also be applicable for immunoradiometric (IRMA) or immunochemiluminescent (ICMA) assays. SUBJECTS AND METHODS: ACTH was measured by RIA, immunoradiometric and/or immunochemiluminescent assay on samples obtained during three types of diagnostic testing in a tertiary referral setting: a) basally (63 CD, 5 AA, 2 EAS and 37 non-CS patients); b) in 44 CD patients following CRH; c) in 6 ectopic CS and 17 CD patients during IPSS. The primary outcome was comparison of diagnostic utility. RESULTS: a) IRMA results, while lower, correlated highly with RIA (r=0.9, p<0.0001) and had similar sensitivity (100 vs 80%) and specificity (89 vs 94%) for the diagnosis of AA (p=0.3); b) the sensitivity for CD of CRH testing using IRMA was similar to that of RIA (85 vs 83%, p=1.0); c) during IPSS, IRMA had similar sensitivity (100%) and specificity (100 vs 83%) compared with ICMA or RIA (p=1.0). CONCLUSIONS: ACTH immunometric assays correlate closely to RIA and offer similar diagnostic utility.