Fig. 2

Identification and characterization of contracted and expanded clones after TNF inhibition. a Number of clones that are significantly contracted and expanded after 12 weeks of TNF inhibition (P < 0.05). Abbreviations: N, number of clones; P, p-value. b In the left side, the average clonal frequency variation detected in contracted and expanded clones is shown at the chain level. The scale of each radar plot break is independent from the others. The size of the chain name is proportional to the statistical significance of the difference of clonal frequency variation between contracted and expanded clones. Chains showing a significantly different clonal frequency variation between contracted and expanded clones are colored in red (P < 0.05). In the right side, the ratio between the average clonal frequency variation detected in contracted and expanded clones is shown. c Biochemical profile of significantly contracted and expanded clones after TNFi therapy. For each chain, the enrichment of the indicated group of clones in each biochemical feature is represented by a circle. The circle is colored according to the degree of biochemical enrichment (i.e., blue) or depletion (i.e., red) compared to a random repertoire from the same chain. The size of the circle is proportional to the statistical significance in the negative logarithmic scale of the enrichment in each biochemical feature. Only significant differences are represented as circles (P < 0.05). Abbreviations: BES, Biochemical Enrichment Score. d Differential biochemical profile resulting from directly contrasting expanded and contracted clones after TNFi therapy. For each chain, the association of clonal contraction/expansion with the indicated biochemical property is represented by a circle. The circle is colored according to the effect direction, ranging from red (i.e., the biochemical feature is lower in contracted clones) to blue (i.e., the biochemical feature is higher in expanded clones). The size of the circle is proportional to the statistical significance of the association in the negative logarithmic scale. Non-significant differences are hidden (P > 0.05). e CDR3 amino acid sequence similarity networks for expanded and contracted IGL clones stratified by clinical response to TNFi therapy. Clones are represented as nodes and edges connect clones differing by at most one amino acid in the CDR3 sequence. The node size is proportional to the number of similarity connections with other clones. The radial width of a given clone is proportional to its number of similarity connections with other clones, so that large clones indicate CDR3 amino acid sequences that are highly similar to those of the other clones within the specified set. Each node is divided into as many fractions as individuals have the clone. f Differential biochemical profile resulting from directly contrasting expanded and contracted clones within each group of responder and non-responder patients to TNFi therapy. The details of the graphical representation are described in d