Comparison of complement gene expression profiles between cases with TA-TMA and controls after autologous HSCT
| Gene . | Children with TA-TMA after autologous HSCT . | Children without TA-TMA after autologous HSCT . | Complement protein function and regulation by interferons (data from Interferon Web site v. 2.01, accessed 24 March 2019) . | ||
|---|---|---|---|---|---|
| Fold change in expression . | Adjusted P . | Fold change in expression . | Adjusted P . | ||
| Gene expression significantly changed only in children with TA-TMA | |||||
| SERPING1 (C1INH) | 5.0 | .0029 | 0.63 | .28 | Inhibits activated C1r and C1S: negative regulator of classical pathway. Upregulated by types I and II interferons. |
| C2 | 2.88 | .00023 | 0.88 | .77 | Necessary component of classical pathway of complement. Upregulated by types I and II interferons. |
| CFD | 1.81 | .05 | 1.12 | .7 | Majority of production is extrahepatic; This protease catalyzes the cleavage of factor B, the rate-limiting step of the alternative pathway of complement activation; a net promoter of complement activation. Upregulated by types I and II interferons in majority of datasets. |
| C5AR1 | 2.3 | .005 | 1.29 | .47 | Binds C5a: Receptor activation stimulates chemotaxis, granule enzyme release, intracellular calcium release and superoxide anion production. Downregulated by types I and II interferons. |
| C5AR2 | 2.08 | .03 | 1.3 | .39 | Receptor for the chemotactic and inflammatory C3a, C4a, and C5a anaphylatoxin peptide. Data mixed on interferon regulation upregulated in 1 and downregulated in 2 datasets. |
| PLAUR | 1.91 | .04 | 1.08 | .88 | Acts as a receptor for urokinase plasminogen activator. Plays a role in localizing and promoting plasmin formation. Downregulated by types I and II interferons. |
| Gene expression significantly changed only in children without TA-TMA | |||||
| C3 | 0.56 | .51 | 0.18 | 9.6 × 10−9 | C3 plays a central role in the activation of the complement system. Processing of C3 by C3 convertase is the central reaction in both classical and alternative complement pathways. Downregulated by types I and II interferons. |
| CFI | 3.2 | .39 | 8.5 | .0049 | Responsible for cleaving the α-chains of C4b and C3b in the presence of the cofactors C4-binding protein and factor H respectively. Negative regulator of complement. Not reported to be regulated by interferons. |
| GENE expression significantly changed in children with and without TA-TMA | |||||
| C1QC | 22.8 | 2.2 × 10−13 | 7.6 | 8.7 × 10−16 | C1QC, B, and A combine to form C1Q, which is the recognition molecule for activation of complement via the classical pathway; majority of production is extrahepatic. Upregulated by interferon-γ. |
| C1QB | 15 | 1.7 × 10−12 | 3.7 | 1 × 10−9 | |
| C1QA | 7.87 | 3.7 × 10−8 | 2.95 | 4 × 10−7 | |
| C3AR1 | 2.66 | .0021 | 2.74 | 5.1 × 10−7 | Receptor for activated C3: binding of C3a by the encoded receptor activates chemotaxis, granule enzyme release, superoxide anion production, and bacterial opsonization. Data mixed on interferon regulation; majority of datasets report upregulation. |
| CR2 | 0.06 | 5.32 × 10−5 | 0.03 | 3.23 × 10−11 | Receptor for C3d, and EBV, participates in B-cell activation. Data mixed on interferon regulation; 1 dataset reports upregulation and 1 downregulation. |
| Gene . | Children with TA-TMA after autologous HSCT . | Children without TA-TMA after autologous HSCT . | Complement protein function and regulation by interferons (data from Interferon Web site v. 2.01, accessed 24 March 2019) . | ||
|---|---|---|---|---|---|
| Fold change in expression . | Adjusted P . | Fold change in expression . | Adjusted P . | ||
| Gene expression significantly changed only in children with TA-TMA | |||||
| SERPING1 (C1INH) | 5.0 | .0029 | 0.63 | .28 | Inhibits activated C1r and C1S: negative regulator of classical pathway. Upregulated by types I and II interferons. |
| C2 | 2.88 | .00023 | 0.88 | .77 | Necessary component of classical pathway of complement. Upregulated by types I and II interferons. |
| CFD | 1.81 | .05 | 1.12 | .7 | Majority of production is extrahepatic; This protease catalyzes the cleavage of factor B, the rate-limiting step of the alternative pathway of complement activation; a net promoter of complement activation. Upregulated by types I and II interferons in majority of datasets. |
| C5AR1 | 2.3 | .005 | 1.29 | .47 | Binds C5a: Receptor activation stimulates chemotaxis, granule enzyme release, intracellular calcium release and superoxide anion production. Downregulated by types I and II interferons. |
| C5AR2 | 2.08 | .03 | 1.3 | .39 | Receptor for the chemotactic and inflammatory C3a, C4a, and C5a anaphylatoxin peptide. Data mixed on interferon regulation upregulated in 1 and downregulated in 2 datasets. |
| PLAUR | 1.91 | .04 | 1.08 | .88 | Acts as a receptor for urokinase plasminogen activator. Plays a role in localizing and promoting plasmin formation. Downregulated by types I and II interferons. |
| Gene expression significantly changed only in children without TA-TMA | |||||
| C3 | 0.56 | .51 | 0.18 | 9.6 × 10−9 | C3 plays a central role in the activation of the complement system. Processing of C3 by C3 convertase is the central reaction in both classical and alternative complement pathways. Downregulated by types I and II interferons. |
| CFI | 3.2 | .39 | 8.5 | .0049 | Responsible for cleaving the α-chains of C4b and C3b in the presence of the cofactors C4-binding protein and factor H respectively. Negative regulator of complement. Not reported to be regulated by interferons. |
| GENE expression significantly changed in children with and without TA-TMA | |||||
| C1QC | 22.8 | 2.2 × 10−13 | 7.6 | 8.7 × 10−16 | C1QC, B, and A combine to form C1Q, which is the recognition molecule for activation of complement via the classical pathway; majority of production is extrahepatic. Upregulated by interferon-γ. |
| C1QB | 15 | 1.7 × 10−12 | 3.7 | 1 × 10−9 | |
| C1QA | 7.87 | 3.7 × 10−8 | 2.95 | 4 × 10−7 | |
| C3AR1 | 2.66 | .0021 | 2.74 | 5.1 × 10−7 | Receptor for activated C3: binding of C3a by the encoded receptor activates chemotaxis, granule enzyme release, superoxide anion production, and bacterial opsonization. Data mixed on interferon regulation; majority of datasets report upregulation. |
| CR2 | 0.06 | 5.32 × 10−5 | 0.03 | 3.23 × 10−11 | Receptor for C3d, and EBV, participates in B-cell activation. Data mixed on interferon regulation; 1 dataset reports upregulation and 1 downregulation. |