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Recent findings demonstrate the common genetic basis for many immune-mediated diseases, and consequently, the partially shared pathogenesis. We collected these findings and reviewed the extension of these overlaps to other disease characteristics. Two autoimmune diseases were selected that also share the specific target organ, the bowel. The etiology and immunopathogenesis of both conditions characterized by chronic intestinal inflammation, inflammatory bowel disease (IBD) and celiac disease (CeD), are not completely understood. Both are complex diseases with genetics and environment contributing to dysregulation of innate and adaptive immune responses, leading to chronic inflammation and disease. CeD constitutes a particular disease because the main environmental and genetic triggers are largely known. IBD comprises two main clinical forms, Crohn's disease and ulcerative colitis, which most likely involve a complex interplay between some components of the commensal microbiota and other environmental factors in their origin. These multifactorial diseases encompass a broad spectrum of clinical phenotypes and ages of onset, although the clinical presentation often differs depending on childhood or adult onset, with greater heterogeneity commonly observed in adults.

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Intrathecal production of kappa free light chains (KFLC) occurs in multiple sclerosis and can be measured using the KFLC index. KFLC index values can be determined more easily than oligoclonal bands (OB) detection and seem more sensitive than the immunoglobulin (Ig)G index to diagnose multiple sclerosis. We assessed the value of OB, KFLC index cut-offs 5.9, 6.6, and 10.61, and IgG index to diagnose multiple sclerosis with prospectively acquired data from a clinically isolated syndrome (CIS) inception cohort. We selected patients with sufficient data to determine OB positivity, MRI dissemination in space (DIS) and time (DIT), IgG index, and sufficient quantities of paired CSF and blood samples to determine KFLC indexes (n = 214). We used Kendall´s Tau coefficient to estimate concordance; calculated the number of additional diagnoses when adding each positive index to DIS and positive OB; performed survival analyses for OB and each index with the outcomes second attack and 2017 MRI DIS and DIT; and estimated the diagnostic properties of OB and the different indexes for the abovementioned outcomes at five years. OB were positive in 138 patients (64.5%), KFLC-5.9 in 136 (63.6%), KFLC-6.6 in 135 (63.1%), KFLC-10.61 in 126 (58.9%) and IgG index in 101 (47.2%). The highest concordance was between OB and KFLC-6.6 (τ=0.727) followed by OB and KFLC-5.9 (τ=0.716). Combining DIS plus OB or KFLC-5.9 increased the number of diagnosed patients by 11 (5.1%), with KFLC-6.6 by 10 (4.7%), with KFLC-10.61 by 9 (4.2%), and with IgG index by 3 (1.4%). Patients with positive OB or indexes reached second attack and MRI DIS and DIT faster than patients with negative results (P < 0.0001 except IgG index in second attack: P = 0.016). In multivariable Cox models [aHR (95% CI)], the risk for second attack was very similar between KFLC-5.9 [2.0 (0.9-4.3), P = 0.068] and KFLC-6.6 [2.1 (1.1-4.2), P = 0.035]. The highest risk for MRI DIS and DIT was demonstrated with KFLC-5.9 [4.9 (2.5-9.6), P < 0.0001], followed by KFLC-6.6 [3.4 (1.9-6.3), P < 0.0001]. KFLC-5.9 and KFLC-6.6 had a slightly higher diagnostic accuracy than OB for second attack (70.5, 71.1, and 67.8) and MRI DIS and DIT (85.7, 85.1, and 81.0). KFLC indexes 5.9 and 6.6 performed slightly better than OB to assess multiple sclerosis risk and in terms of diagnostic accuracy. Given the concordance between OB and these indexes, we suggest using DIS plus positive OB or positive KFLC index as a modified criterion to diagnose multiple sclerosis.

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