Fig. 1: Orthologous TNIP1 missense variant in patients and mice with systemic autoimmunity.
From: A TNIP1-driven systemic autoimmune disorder with elevated IgG4
a,b, TNIP1Q333P variant in families (a) and results from Sanger sequencing (b). c, Position of the Q333P variant within the TNIP1 protein domains. d, Conservation across species. e, AlphaFold2-generated structure of canonical TNIP1 (AF-Q15025-F1) as modeled in PyMOL. Residue 333 is indicated in blue. The red arrow indicates the P333-disrupted hydrogen bonding in the alpha-helix 4 backbone f, Patient immunoglobulin IgG concentrations compared to the ‘normal’ population ranges (shaded boxes) as defined by the Canberra Hospital (Australia) and Renji Hospital (Shanghai, China) pathology laboratories, respectively. g, Serum antibodies to DNA from 20–28-week-old male (n = 8) and female (n = 19) vikala mice; Tnip1+/+ (n = 6), Tnip1vik/+ (n = 14) and Tnip1vik/vik (n = 7) mice by enzyme-linked immunosorbent assay (ELISA). Optical density at 405 nm (OD405). h, Total serum IgG in 12-week-old male (n = 10) and female (n = 10) vikala mice by ELISA; Tnip1+/+ (n = 7), Tnip1vik/+ (n = 7) and Tnip1vik/vik (n = 6). Each point represents a mouse (biological replicate). i, Meso Scale Discovery readout for IgG subclasses (pg ml−1) in 20–22-week-old male (n = 9) and female (n = 9) vikala mice; Tnip1+/+ (n = 6), Tnip1vik/+ (n = 6) and Tnip1vik/vik (n = 6); each point represents a mouse (biological replicate). j, H&E staining showing lymphocytic infiltrates in the submandibular salivary glands of 20–28-week-old vikala mice; Tnip1+/+ (n = 10), Tnip1vik/+ (n = 11) and Tnip1vik/vik (n = 8). Scale bar, 100 μm. k, Focus score indicating the severity of lymphocytic infiltration per tissue section; each dot represents a mouse (biological replicate). Infiltrates are defined as foci consisting of 50 or more mononuclear cells. Scores: 0, no infiltrates; 1, one focal infiltrate; 2, multiple focal infiltrates. The medians are indicated by the black line, the mouse sex is indicated by the symbol type (g–i,k). In g,h,j, data are representative of n = 2 experiments. Data in i was from an experiment performed once; scoring in k was performed once. Statistical significance was calculated using a one-way analysis of variance (ANOVA) with multiple comparisons using a Tukey test after log-transformation of the data. Exact P values are shown. NS, not significant.
