M. Gariglio

Characterization of skin lesions induced by skin‐tropic α‐ and β‐papillomaviruses in a patient with epidermodysplasia verruciformis

Epidermodysplasia verruciformis (EV) is a rare, lifelong, autosomal recessive skin disease associated with an unusual susceptibility to infections with ubiquitous β‐human papillomaviruses (β‐HPVs), and in some cases also skin‐tropic α genotypes. In this case report, HPV infection patterns were correlated with pathology and clinical manifestations of skin lesions from a patient with EV, without loss‐of‐function mutations in the EVER genes. HPV infection was investigated by both polymerase chain reaction (PCR) and laser capture microdissection (LCM) PCR, alongside immunofluorescence for the viral proteins E4 and L1. Analysis of eyebrow hair bulbs revealed multiple β‐genus HPV infections, including HPV20 and HPV24, which were consistently found in all 11 skin lesions on the patient. Six lesions were also positive for the skin tropic α‐genotype, HPV27. Clear‐cut differences between two wart‐like lesions, one caused by a skin‐tropic α‐genotype and the other by β‐genotypes (as detected by LCM PCR) are shown, including the high cellular proliferation rate in β‐HPV‐induced lesions. Widespread expression of the early protein E4 was also evident in skin lesions positive for HPV20 by LCM PCR in both tumours and nearby intraepidermal proliferative areas. L1 expression was restricted to areas of intraepidermal proliferation showing productive infection. The patients inability to control HPV infections is conclusive to the uncontrolled replication of few genotypes from both α and β genera, which cause proliferative lesions with clear‐cut clinical and histological features.

Analysis of human β-papillomavirus and Merkel cell polyomavirus infection in skin lesions and eyebrow hair bulbs from a cohort of patients with chronic lymphocytic leukaemia.

Research demonstrates an increased incidence of skin cancer in immunocompromised hosts, including patients with chronic lymphocytic leukaemia (CLL) and organ transplant recipients (OTRs). Active human β‐papillomavirus (β‐HPV) infection has been found in OTR skin lesions, suggesting its possible involvement in skin carcinogenesis. Merkel cell polyomavirus (MCPyV) has also been reported in cases of skin cancer.

Chapter 40 – IFI16 Autoantibodies

IFI16 belongs to the interferon (IFN)-inducible HIN-200/Ifi-200 gene family, which encodes evolutionary related human (IFI16, IFIX, MNDA, and AIM2) and murine (Ifi202a, Ifi202b, Ifi203, Ifi204, Ifi205/D3, and Ifi206) nuclear phosphoproteins. To detect anti-IFI16 antibodies in the sera from patients affected by autoimmune disorders, a semiquantitative enzyme-linked immunosorbent assay (ELISA) was generated and characterized using a recombinant purified IFI16 protein as antigen. Anti-IFI16 titers above the 95th percentile for control subjects were observed in more than 50% of systemic lupus erythematosus (SLE) patients, 30% of systemic sclerosis (SSc) patients, and 25% of Sjogren syndrome (SjS) patients versus 6% of healthy donors. Anti-IFI16 antibodies were detected in 30% of the SSc patients who tested negative for both anticentromere (ACA) and anti-topo I (anti-Scl 70) antibodies. In this subgroup of patients, anti-IFI16 were significantly associated with the limited cutaneous form of SSc with a sensitivity of 40% and a specificity of 81%. Moreover, analysis of the distribution of anti-RNAP II antibodies versus anti-IFI16 in the same SSc population showed that they were mutually exclusive. Finally, anti-IFI16 were also significantly associated with heart involvement. In SLE patients, the prevalence and titers of anti-IFI16 antibodies were significantly higher in patients without renal involvement than in patients with glomerulonephritis (63% and 24%, respectively). Anti-IFI16 antibodies inversely correlated with proteinuria at univariate analysis and with C3 hypocomplementemia at univariate and multivariate analysis, including SLEDAI and anti-double-stranded deoxyribonucleic acid (dsDNA) as measures of disease activity. Although further studies are needed to clarify the exact mechanisms of the function of anti-IFI16 antibodies, these antibodies may serve as a new biomarker to be used in the diagnosis and assessment of disease activity in patients with SSc or SLE, with or without renal involvement.

La rispostain vivo alľinterleron-α/β

(IFN-α/β) fu valutata misurando ľinduzione di alcuni RNA messaggeri (mRNA) IFN-inducibili in topi DBA/2 inoculati con poli I:C. Utilizzando sonde di cDNA. omologhe alľmRNA dei seguenti geni: 202, 2′-5′ oligoadenilatosintetasi (2-5A sintetasi) ed H-2, si e osservato un significativo aumento di mRNA nella milza e nel midollo a 6 ore dalľinoculo intraperitoneo (i.p.) del poli I:C. Gli mRNA raggiungevano il loro massimo livello di espressione tra le 12 e le 24 ore dalľinoculo per poi decrescere gradatamente. Il pretrattamento con anticorpi anti-IFN-α/β di murino riduceva di circa il 60% ľaumento di mRNA. Nel loro insieme questi risultati dimostrano che anchein vivo gli IFN sono in grado di aumentare ľespressione di alcuni geni.Regulation of gene expression in vivoby interferons.In vivo responses to interferon-α/β (IFN-α/β) in mice were determined by measuring the steady-state levels of induced mRNAs following injection of poly I:C. With cDNA probes for mouse 202, 2′-5′ oligoadenylate synthetase and H-2 an increase of the corresponding mRNAs in the spleen and in the bone marrow was observed as early as 6 hours after poly I:C injection. Maximal levels of mRNA expression were reached between 12 and 24 hours after the injection, followed by a gradual decrease. Pretreatment of mice with anti-mouse IFN-α/β significantly impaired mRNA induction by poly I:C. Altogether these results suggest that alsoin vivo IFN-α/β may increase gene expression.Riassunto(IFN-α/β) fu valutata misurando ľinduzione di alcuni RNA messaggeri (mRNA) IFN-inducibili in topi DBA/2 inoculati con poli I:C. Utilizzando sonde di cDNA. omologhe alľmRNA dei seguenti geni: 202, 2′-5′ oligoadenilatosintetasi (2-5A sintetasi) ed H-2, si è osservato un significativo aumento di mRNA nella milza e nel midollo a 6 ore dalľinoculo intraperitoneo (i.p.) del poli I:C. Gli mRNA raggiungevano il loro massimo livello di espressione tra le 12 e le 24 ore dalľinoculo per poi decrescere gradatamente. Il pretrattamento con anticorpi anti-IFN-α/β di murino riduceva di circa il 60% ľaumento di mRNA. Nel loro insieme questi risultati dimostrano che anchein vivo gli IFN sono in grado di aumentare ľespressione di alcuni geni.