Genotype, age, and proportion of B-cell subsets in the cohort of patients deficient for specific TLRs or molecules that impair the TLR/IL1R-signaling pathways
| Deficiency . | Patient . | Mutation . | Reference . | Age, y* . | % CD19+ . | IgD+CD27+ (% of B cells) . | IgD−CD27+ (% of B cells) . | IgM-only CD27+ (% of IgD-CD27+)† . | IgA+CD27+ (% of B cells) . | DN IgD−CD27− (% of B cells) . | Transitional 19+24++38++ (% of B cells) . |
|---|---|---|---|---|---|---|---|---|---|---|---|
| IRAK-4 | P30 | M1V/1188 + 520A > G | 29 | 2 | 20 | 2.5 | 6.2 | 3.1 | 1 | 2.7 | 7 |
| 2.5 | 28 | 0.8 | 2.9 | nd | 0.4 | 7.7 | nd | ||||
| IRAK-4 | P8 | 1189-1G > T/ 1188 + 520A > G | 29 | 4 | 22 | 4 | 11 | 5.3 | nd | 4.5 | nd |
| 8.5 | 21 | 1.4 | 5.8 | nd | 1.65 | 4 | nd | ||||
| 9 | 11 | 2.4 | 8 | 1.8 | 2.44 | 2.8 | 2.43 | ||||
| IRAK-4 | P15 | 1-1096_40 + 23del / 1-1096_40 + 23del | 29 | 7 | 28 | 1.3 | 8.9 | nd | 1.65 | 8.2 | nd |
| 9.5 | nd | 3.3 | 16.3 | 4 | 2.4 | 3 | 7 | ||||
| IRAK-4 | P13 | E402X/E402X | 29 | 10 | 8 | 2.4 | 7.3 | 5.8 | nd | 2.1 | 6 |
| IRAK-4 | P2 | Q293X/ BAC210N13del | 29 | 12 | nd | 3 | 11 | 5.1 | nd | 4.2 | nd |
| 16.5 | 15 | 1.4 | 3.7 | nd | nd | 7.5 | nd | ||||
| IRAK-4 | P48 | Q293X/Q293X | 29 | 12 | nd | 6 | 11 | nd | nd | 3.7 | 8 |
| IRAK-4 | P24 | 1240insA/9421481_ 1125 + 547del | 29 | 16 | nd | 6.6 | 7.4 | nd | 1.8 | 1.5 | 10 |
| IRAK-4 | P31 | R12C/831 + 5G > T | 29 | 17 | nd | 3.7 | 16 | nd | 5.2 | 5.6 | 5 |
| IRAK-4 | P17 | Q293X/Q293X | 29 | 25 | 20 | 1.8 | 7.7 | nd | 1 | 8 | nd |
| MyD88 | P2 | R209C/L106P | 29 | 2 | 18 | 2.8 | 6.7 | 4.8 | 1.9 | 4 | 7 |
| MyD88 | P6 | E65del/E65del | 29 | 4.5 | 19 | 4.6 | 7.7 | 6.7 | 1.7 | 2.3 | 12.4 |
| MyD88 | P5 | E65del/E65del | 29 | 7 | 17 | 5.4 | 9.2 | 4.3 | 3 | 2.7 | 22 |
| MyD88 | P3 | R209C/R209C | 29 | 9 | 8 | 9 | 15.5 | 2.3 | 2.5 | 5 | 5.7 |
| 9.5 | 11 | 5.8 | 12 | nd | 2.8 | 11.4 | 5 | ||||
| 10.5 | 5.5 | 5.6 | 7.6 | 1.7 | 1.5 | 3.3 | 13 | ||||
| MyD88 | P4 | R209C/R209C | 29 | 16 | 13 | 6 | 21 | nd | 7.2 | 9.6 | 5 |
| UNC-93B | P1 | 1034 del4/1034 del4 | 24 | 16 | 23 | 8.4 | 7.7 | 7.4 | 2.5 | 2.5 | 4.4 |
| UNC93-B | P2 | G781A/G781A | 24 | 15 | 23 | 15 | 14 | 4.7 | 5.1 | 5.6 | 4.4 |
| TLR3 | P1 | P554S/wt‡ | 30 | 15 | 17 | 14 | 9 | 4.5 | 2.5 | 1.7 | 5.6 |
| TLR3 | P2 | E746X/P554S | 31 | 19 | 12 | 11.5 | 6.5 | nd | 2 | 7 | 1.7 |
| TRIF | P1 | R141X/R141X | 27 | 3.5 | 22 | 4.6 | 5.5 | nd | 0.6 | 15 | 35 |
| TIRAP | R2 | R121W/R121W | § | 15 | 6.3 | 3.8 | 18.4 | 2.1 | 6 | 10 | 4.5 |
| TIRAP | R3 | R121W/R121W | § | 20 | 7.5 | 3 | 17.5 | 1.8 | 5.8 | 6.5 | 5.2 |
| TIRAP | R1 | R121W/R121W | § | 22 | 17 | 1.8 | 6.5 | nd | 1.6 | 5.6 | 7 |
| TIRAP | R4 | R121W/R121W | § | 23 | 11 | 2.6 | 10.5 | 1.8 | 3.7 | 7.8 | 4.6 |
| Controls | Normal values¶ | 2-3 | 20.8 | 5.4 | 2.6 | nd | nd | 2.5 | 8.7 | ||
| 4-5 | 16.1 | 6.5 | 5.6 | nd | nd | 4.5 | 7.3 | ||||
| 6-10 | 12.2 | 10 | 6.5 | nd | nd | 5 | 6 | ||||
| 11-18 | 13.3 | 7.3 | 5.4 | nd | nd | 3.7 | 5.6 | ||||
| 19-25 | 9.1 | 11.7 | 9.4 | nd | nd | 3.2 | 4.7 | ||||
| Normal values# | 2-5 | 1.31 | |||||||||
| 6-10 | 2.44 | ||||||||||
| 11-15 | 2.93 | ||||||||||
| > 16 | 3.11 |
| Deficiency . | Patient . | Mutation . | Reference . | Age, y* . | % CD19+ . | IgD+CD27+ (% of B cells) . | IgD−CD27+ (% of B cells) . | IgM-only CD27+ (% of IgD-CD27+)† . | IgA+CD27+ (% of B cells) . | DN IgD−CD27− (% of B cells) . | Transitional 19+24++38++ (% of B cells) . |
|---|---|---|---|---|---|---|---|---|---|---|---|
| IRAK-4 | P30 | M1V/1188 + 520A > G | 29 | 2 | 20 | 2.5 | 6.2 | 3.1 | 1 | 2.7 | 7 |
| 2.5 | 28 | 0.8 | 2.9 | nd | 0.4 | 7.7 | nd | ||||
| IRAK-4 | P8 | 1189-1G > T/ 1188 + 520A > G | 29 | 4 | 22 | 4 | 11 | 5.3 | nd | 4.5 | nd |
| 8.5 | 21 | 1.4 | 5.8 | nd | 1.65 | 4 | nd | ||||
| 9 | 11 | 2.4 | 8 | 1.8 | 2.44 | 2.8 | 2.43 | ||||
| IRAK-4 | P15 | 1-1096_40 + 23del / 1-1096_40 + 23del | 29 | 7 | 28 | 1.3 | 8.9 | nd | 1.65 | 8.2 | nd |
| 9.5 | nd | 3.3 | 16.3 | 4 | 2.4 | 3 | 7 | ||||
| IRAK-4 | P13 | E402X/E402X | 29 | 10 | 8 | 2.4 | 7.3 | 5.8 | nd | 2.1 | 6 |
| IRAK-4 | P2 | Q293X/ BAC210N13del | 29 | 12 | nd | 3 | 11 | 5.1 | nd | 4.2 | nd |
| 16.5 | 15 | 1.4 | 3.7 | nd | nd | 7.5 | nd | ||||
| IRAK-4 | P48 | Q293X/Q293X | 29 | 12 | nd | 6 | 11 | nd | nd | 3.7 | 8 |
| IRAK-4 | P24 | 1240insA/9421481_ 1125 + 547del | 29 | 16 | nd | 6.6 | 7.4 | nd | 1.8 | 1.5 | 10 |
| IRAK-4 | P31 | R12C/831 + 5G > T | 29 | 17 | nd | 3.7 | 16 | nd | 5.2 | 5.6 | 5 |
| IRAK-4 | P17 | Q293X/Q293X | 29 | 25 | 20 | 1.8 | 7.7 | nd | 1 | 8 | nd |
| MyD88 | P2 | R209C/L106P | 29 | 2 | 18 | 2.8 | 6.7 | 4.8 | 1.9 | 4 | 7 |
| MyD88 | P6 | E65del/E65del | 29 | 4.5 | 19 | 4.6 | 7.7 | 6.7 | 1.7 | 2.3 | 12.4 |
| MyD88 | P5 | E65del/E65del | 29 | 7 | 17 | 5.4 | 9.2 | 4.3 | 3 | 2.7 | 22 |
| MyD88 | P3 | R209C/R209C | 29 | 9 | 8 | 9 | 15.5 | 2.3 | 2.5 | 5 | 5.7 |
| 9.5 | 11 | 5.8 | 12 | nd | 2.8 | 11.4 | 5 | ||||
| 10.5 | 5.5 | 5.6 | 7.6 | 1.7 | 1.5 | 3.3 | 13 | ||||
| MyD88 | P4 | R209C/R209C | 29 | 16 | 13 | 6 | 21 | nd | 7.2 | 9.6 | 5 |
| UNC-93B | P1 | 1034 del4/1034 del4 | 24 | 16 | 23 | 8.4 | 7.7 | 7.4 | 2.5 | 2.5 | 4.4 |
| UNC93-B | P2 | G781A/G781A | 24 | 15 | 23 | 15 | 14 | 4.7 | 5.1 | 5.6 | 4.4 |
| TLR3 | P1 | P554S/wt‡ | 30 | 15 | 17 | 14 | 9 | 4.5 | 2.5 | 1.7 | 5.6 |
| TLR3 | P2 | E746X/P554S | 31 | 19 | 12 | 11.5 | 6.5 | nd | 2 | 7 | 1.7 |
| TRIF | P1 | R141X/R141X | 27 | 3.5 | 22 | 4.6 | 5.5 | nd | 0.6 | 15 | 35 |
| TIRAP | R2 | R121W/R121W | § | 15 | 6.3 | 3.8 | 18.4 | 2.1 | 6 | 10 | 4.5 |
| TIRAP | R3 | R121W/R121W | § | 20 | 7.5 | 3 | 17.5 | 1.8 | 5.8 | 6.5 | 5.2 |
| TIRAP | R1 | R121W/R121W | § | 22 | 17 | 1.8 | 6.5 | nd | 1.6 | 5.6 | 7 |
| TIRAP | R4 | R121W/R121W | § | 23 | 11 | 2.6 | 10.5 | 1.8 | 3.7 | 7.8 | 4.6 |
| Controls | Normal values¶ | 2-3 | 20.8 | 5.4 | 2.6 | nd | nd | 2.5 | 8.7 | ||
| 4-5 | 16.1 | 6.5 | 5.6 | nd | nd | 4.5 | 7.3 | ||||
| 6-10 | 12.2 | 10 | 6.5 | nd | nd | 5 | 6 | ||||
| 11-18 | 13.3 | 7.3 | 5.4 | nd | nd | 3.7 | 5.6 | ||||
| 19-25 | 9.1 | 11.7 | 9.4 | nd | nd | 3.2 | 4.7 | ||||
| Normal values# | 2-5 | 1.31 | |||||||||
| 6-10 | 2.44 | ||||||||||
| 11-15 | 2.93 | ||||||||||
| > 16 | 3.11 |
DN indicates double negative; IRAK-4, IL-1 receptor–associated kinase 4; and nd, not determined.
Age at analysis.
IgM-only CD27+ cells represent on average 7.9% ± 1.6% of the IgD−CD27+ subset in healthy adult controls.4
The P554S allele is loss-of-function and dominant negative.
R1 to R4 are relatives of a TIRAP deficient patient (proband); they have a confirmed TIRAP deficiency but no clinical phenotype (L.I. and J.-L.C., unpublished data, 2012)
Reference values (median) are taken from Morbach et al.32
Reference values for the IgA+CD27+ B-cell subset (mean) are from Dr Menno Van Zelm, Netherlands, (Erasmus Medical Center, Rotterdam, The Netherlands; personal written communication, January 2012).