Textbook of Personalized Medicine - Second Edition [2015]

(Ron) #1

554


treatments. Several clinical studies have tested new therapies directly targeting B
lymphocytes. Flow cytometry of circulating peripheral B lymphocytes have been
used to defi ne pathogenic subsets of the disease and assess therapeutic effi cacy.
Biomarkers for SLE include Fc receptor genes (disease susceptibility), complement
C4d-bound erythrocytes (diagnosis or disease activity), CD27 plasma cells (disease
activity), ‘interferon signature’ (disease activity), and anti-C1q antibodies (disease
activity and organ involvement). These promising candidate biomarkers need to be
validated through rigorous, large-scale multicenter studies. There is still an urgent
need for better biomarkers and pharmacodiagnostic tests with which to monitor dis-
ease activity in patients with SLE and response to treatment.
Lupus Therasight™ (PIKAMAB) is a proprietary approach to stratify patients
based on the FcGR-3A, 2A, 3B, and 2B polymorphisms. These polymorphisms,
when collectively correlated, should provide a deeper understanding on the mecha-
nism of onset and progression of lupus and lupus nephritis, and can determine the
severity of these diseases in patients irrespective of their ethnicity. The test, which
includes a functional assay, can provide signifi cant clues with regard to the progres-
sion and severity of these diseases in these patients over a period of time.


Personalized Therapy of Rheumatoid Arthritis


Rheumatoid arthritis (RA) is a multicomplex system infl ammatory disorder, which
affects the synovial lining of the joints and tendons. As a result of treatment strate-
gies based upon individualized measurement of disease activity, the clinical view of
RA has changed from a destructive autoimmune disease to a condition in which
signifi cant damage can be prevented in the majority of patients. Although the cause
of RA is not known, factors such as genes, epigenetics, environments, local joint
characteristics or processes of aging might infl uence the clinical phenomenon RA
(Pieringer and Studnicka-Benke 2013 ). Environmental factors are generally consid-
ered to play a role with systemic immune reactions precipitating a cascade of
infl ammatory reactions. Consideration of all of these factors is important for plan-
ning a personalized approach to management of RA.


Genetics and Epigenetic Aspects of Rheumatoid Arthritis


Hyperproduction of interleukin-6 (IL-6) is observed in RA patients and serum level
of IL-6 is closely related to disease activity. IL-6 is a pleiotropic cytokine and its
hyperfunctions explain most of the clinical symptoms in RA. Although RA has a
complex mode of inheritance, HLA-DRB1 and PTPN22 are well-established sus-
ceptibility loci. A common genetic variant at the TRAF1-C5 locus on chromosome
9 is associated with an increased risk of anti-CCP-positive RA (Plenge et al. 2007 ).
Epigenetics, particularly DNA methylation, is a potential mediator of genetic risk
in RA. A study has compared newly diagnosed RA patients and healthy controls,


17 Personalized Approaches to Immune Disorders
Free download pdf