Research Proposal Form

Application for access to data collected in theUKPID online database

Applicant: / Dr Peter Arkwright
Title of study: / T-cell phenotype as a marker of morbidity and mortality in children and adults with CVID
Condition: / CVID
Current evidence and need for a study: / Background: CVID is a group of PID disorders defined by lower than normal serum immunoglobulin concentrations. It is classically viewed as an antibody immunodeficiency. Despite adequate immunoglobulin replacement patient morbidity and mortality is variable and a number of complications are not those typically seen in pure antibody PID e.g. XLA.
Hypothesis: T-cell rather than B-cell phenotype determines outcome in patients with CVID and patients with low T-cell numbers/function will have the poorest outcome.
Impact: Development of more accurate markers will allow clinicians to provide their patients with better information regarding national history and may lead to more effective therapies for a subgroup of patients with CVID.
National support: This project is supported by aUK NIHR Rare Diseases Collaborative Research Collaboration Grant with Dr Hans Strauss and Dr Peter Arkwright as lead investigators (attached).
Objective(s): / Determine if T-cell phenotype (absolute T-cell numbers and function) correlate with patient outcome in CVID.
  • Primary
/ Correlate absolute T-cell numbers (CD3, CD4, CD8) with mortality, autoimmune / autoinflammatory, granulomatous and severe / disseminated viral diseases.
  • Secondary
/ Correlate lymphocyte function (PHA mitogenesis, other markers of T-cell function) with mortality and morbidity as detailed in the box above.
In/exclusion criteria:
  • Inclusion
/ Children and adults with CVID, defined by ESID/PAGID as (1)
hypogammaglobulinemia with IgG levels two standard
deviations below the mean; (2) impaired vaccine responses
and (3) exclusion of other causes of hypogammaglobulinemia.
  • Exclusion
/ Patients not fitting the above criteria.
Patients in whom laboratory tests detailed above are not available.
Planned study duration: / November 2013 to November 2015

1 It is important that the study concept is discussed with a statistician prior to initiating data extraction and analysis.

Please add the following information:

  1. Previous experience in research in primary immunodeficiencies (list 3 relevant publications)

I am accredited by the GMC/RCPCH as a specialist in paediatric immunologist and have worked as a specialist leading the paediatric immunodeficiency service for Manchester and the North West of England for the last 11 years. I am also a senior lecturer in paediatric immunology at the University of Manchester and have over 100 peer-reviewed publications, many of which relate to PID. I am the lead investigator for Manchester for the ESID registry.

  1. Edgar JD, Buckland M, Guzman D, Conlon NP, Knerr V, Bangs C, Reiser V, Panahloo Z, Workman S, Slatter M, Gennery AR, Davies EG, Allwood Z, Arkwright PD,Helbert M, Longhurst HJ, Grigoriadou S, Devlin LA, Huissoon A, Krishna MT, Hackett S, Kumararatne DS, Condliffe AM, Baxendale H, Henderson K, Bethune C, Symons C, Wood P, Ford K, Patel S,Jain R, Jolles S, El-Shanawany T, Alachkar H, Herwadkar A, Sargur R, ShrimptonA, Hayman G, Abuzakouk M, Spickett G, Darroch CJ, Paulus S, Marshall SE, McDermott EM, Heath PT, Herriot R, Noorani S, Turner M, Khan S, Grimbacher B.The United Kingdom Primary Immune Deficiency (UKPID) Registry: Report of the first 4 years’ activity 2008-2012. Clin Exp Immunol 2013; Jul 11.
  2. Crawford G, Enders A, Gileadi U, Stankovic S, Zhang Q, Lambe T, Crockford TL, Lockstone HE, Freeman A, Arkwright PD, Smart JM, Ma CS, Tangye SG, Goodnow CC, Cerundolo V, Godfrey DI, Su HC, Randall KL, Cornall RC.DOCK8 is critical for the survival and function of NKT cells.Blood 2013122:2052-61.
  3. Jolles S, Williams P, Carne E, Mian H, Huissoon A, Wong G, Hackett S, Lortan J, Platts V, Longhurst H, Grigoriadou S, Dempster J, Deacock S, Kahn S, Darroch J, Simon C, Thomas M, Pavaladurai V, Alachkar H, Herwadker A, Abinun M, Arkwright P, Tarzi M, Helbert M, Bangs C, Pastacaldi C, Phillips C, Bennett H, El-Shanawany T. A UK National Audit of Hereditary and Acquired Angioedema.Clin Exp Immunol 2013 Jun 21.
  1. A disclosure statement regarding potential conflicts of interest (such as financial affiliations with pharmaceutical companies).

I declare no conflict of interests, financial or otherwise.
Evaluation criteria for registry research proposals (1-5 points each):

  • Is the proposal within the scope of the UKPIDDatabase?
  • Does this proposal address an important problem?
  • Are the conceptual or clinical framework, design, methods, and analyses adequately developed, and appropriate to the aims of the proposal? Is the study feasible?
  • Is the proposal original and innovative?
  • Are the investigators appropriately trained and suited to carry out this work? Does the scientific environment in which the work will be done contribute to the probability of success? One of the investigators should be a recognized specialist in the subject.

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