T cells are involved in the pathogenesis of rheumatoid arthritis (RA). CD6 is a co-stimulatory molecule, predominantly expressed on lymphocytes, that has been linked to autoreactive responses. The purpose of this study was to evaluate the safety, immunogenicity and preliminary efficacy of itolizumab, a humanized anti-CD6 monoclonal antibody, in patients with active rheumatoid arthritis. Fifteen patients were enrolled in a phase I, open-label, dose-finding study. Five cohorts of patients received a weekly antibody monotherapy with a dose-range from 0.1 to 0.8 mg/kg. Itolizumab showed a good safety profile, with no severe or serious adverse events reported so far. No signs or symptoms associated with immunosuppression were observed in the study. Objective clinical responses were achieved in more than 80% of patients after treatment completion, and these responses tend to be sustained afterwards. This clinical study constitutes the first evidence of the safety and positive clinical effect of a monotherapy using an anti-CD6 antibody in patients with rheumatoid arthritis.

Mazorra (2014) Immunological and histological evaluation of clinical samples from psoriasis patients treated with anti-CD6 itolizumab, mAbs, 6:3, 782-792,

The CD6 molecule is a pan T cell marker involved in T cell regulation. Although CD6 expression has been correlated with human autoimmune diseases, only a few therapeutic approaches are exploring this molecule as target in the clinic. The biological functions and mechanisms of actions of CD6 have not been definitively established. It is probable that this molecule plays a dual role as a modulator of intracellular signaling. Itolizumab is a humanized monoclonal antibody specific for human CD6, developed at the Center of Molecular Immunology in Havana, Cuba. Its parent murine antibody, the IOR-T1 mAb, had been obtained in the 80's at the Institute of Oncology and Radiology, also in Havana. This article provides an overview of the clinical data obtained in Cuban patients with autoimmune diseases who have been treated with IOR-T1 mAb or itolizumab. Furthermore, we discuss the possible mechanism of action of itolizumab basing the analysis on recent site mutagenesis and structural data, which, contrary to previous interpretations, points to a steric blocking of the CD6-CD166 interaction in the cellular context. Overall, the conducted clinical studies have demonstrated that itolizumab has favorable clinical effects and a safety profile when used as monotherapy in patients with rheumatoid arthritis and psoriasis. So far, in vitro and in vivo evidences indicate that itolizumab has immunomodulatory and anti-inflammatory effects. Hence, itolizumab represents a new therapeutic option for autoimmune diseases such as rheumatoid arthritis and psoriasis.

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Introduction: Autism spectrum disorder (ASD) is a heterogeneous group of neurodevelopmental disorders with complex multifactorial etiologies. Medical comorbidities are common in ASD and include functional gastrointestinal disorders (fGID), which are reported in 30–70% of patients. In this research study, we aimed to systematically assess the prevalence of gastrointestinal problems in ASD and describe their clinical correlates. Methods: In this retrospective study, we reviewed the medical records of all patients admitted to the Comprehensive Medical Program for ASD (AMITEA) at Gregorio Marañón University General Hospital from January 2012 to December 2015. All patients fulfilled the clinical criteria for ASD (DSM-IV-TR). In addition to fGID, epidemiological and clinical variables were collected at intake. Clinical and demographic features were compared among subjects with and without comorbid gastrointestinal problems. Results: The analyses included all patients with documented information about presence/absence of fGID ( n = 845; 95% of patients). Ages ranged from 1 to 53 years (mean = 10.52; SD = 8.92; 80.4% males). At least one fGID was present in 30.5% of patients, constipation being the most prevalent (47.4% of fGID patients); fGID were significantly associated with intellectual disability (ID) ( p = 0.017), sleep disorders ( p = 0.012), and prescription of psychopharmacological treatment ( p = 0.019). Conclusions: Almost one-third of ASD patients in our sample had at least one fGID. The presence of fGID was associated with ID, sleep problems and with behavioral problems (as measured by the prescription of psychotropic drugs). This subsample of ASD patients with fGID deserves particular attention in future research projects, focusing on specific phenotypic characteristics and overlapping biological markers that may underlie both pathologies.