Dissecting the Genetic Architecture of Chronic Inflammatory Demyelinating Polyradiculoneuropathy (CIDP)

1. Specific aim 1: Characterize the genetic architecture of CIDP by using a genome-wide association study (GWAS) approach in a large cohort of CIDP patients and healthy controls, thus defining the 1) Specific aim 1: Characterize the genetic architecture of CIDP by using a genome-wide association study (GWAS) approach in a large cohort of CIDP patients and healthy controls, thus defining the spectrum of single common variants or their combinations (in terms of haplotypes or risk score) predisposing to the disease.

Hypothesis: The frequency of specific alleles/haplotypes in patients with CIDP is significantly different compared to that of the general population.

Approach: We will genotype >700,000 single nucleotide polymorphisms (SNPs) by using the Illumina Global Screening Array (GSA), of approximately 1000 patients with CIDP. About 3500 healthy controls from the Italian population have been already genotyped using GWAS from our genetic department (Prof. Asselta, Humanitas Research Institute, Milan). 2. Specific aim 2: Explore the role of specific alleles/haplotypes in determining the clinical and immunological variability, severity, and therapeutic response of CIDP.

Hypothesis: The genetic architecture of patients with typical CIDP is -at least in part- distinct from that of the CIDP variants; specific alleles/haplotypes associate with intermediate phenotypes, such as the presence of antibodies anti-NF155, anti-NF186, CNTN1, anti-gangliosides; Specific alleles/haplotypes correlate with severity and treatment-response of CIDP.

Approach: Alleles/haplotypes evidence through GWAS will be compared between patients with typical CIDP and its variants, between CIDP patients with and without specific antibodies, between CIDP patients with low and high levels of disability and between CIDP patients with and without response to each individual treatment (IVIg, steroids, plasma exchange) in order to determine whether genetics play a role in determining these phenotypes. 3. Specific aim 3: Verify possible overlaps between CIDP and other autoimmune diseases.