Table 3.
CIS Patient Summary and Signature Score Predictions
| Subject No.a |
Time to LPb |
MRI Brain Lesions |
OCB | CD19/ CD138c |
CD19 VH4 biasd |
CD138 VH4 biasd |
Signature Scoree |
Prediction based on signature score |
Definite MS |
Time to MS Diagnosisf |
|---|---|---|---|---|---|---|---|---|---|---|
| CIS132 | 1 | GD+ | Yes | 19/NA | No | NA | 12.1 | CDMS | Clinical | 18 |
| CIS429 | 1 | GD+ | Yes | 56/NA | No | NA | 15.0 | CDMS | Clinical | 3 |
| CIS3-1 | 2 | WML | Yes | 24/76 | Yes | Yes | 15.5 | CDMS | MRI | 3 |
| ON3-3 | 4 | GD+ | Yes | 39/13 | No | No | 11.3 | CDMS | Clinical | 3 |
| ON3–5 | 1.75 | GD+ | Yes | 35/44 | Yes | Yes | 12.8 | CDMS | Clinical | 2 |
| ON4–7 | 3 | Noneg | Yes | 17/20 | No | Yes | 10.2 | CDMS | Clinical | 5 |
| ON4–8 | 1.5 | WML | Yes | NA/18 | NA | Yes | 9.6 | CDMS | Clinical | 5 |
| ON5-2 | 1 | GD+ | Yes | 29/12 | Yes | Yes | 7.9 | CDMS | Clinical | 3 |
| ON3-1 | 10 | WML | Yes | 23/45 | No | No | 6.4 | No | - | NA |
| ON4–10 | 1.25 | WML | No | 31/NA | No | NA | 2.2 | No | - | NA |
| ON3–4 | 1.5 | Noneg | No | 28/NA | No | NA | 11.3 | CDMS | - | NA |
Abbreviations in table: CIS, Clinically Isolated Syndrome; ON, Optic Neuritis; LP, lumbar puncture; GD, gadolinium enhancing lesion positive; WML, white matter lesions by T2; OCB, oligoclonal bands; CDMS, clinically definite MS; NA, not applicable
CIS132 and CIS429 were generated at UTSWMC; the remaining patient CSF B cell repertoires were generated at UCD.
months from first demyelinating event to LP
Values given are number of unique sequences in CD19 repertoire/CD138 repertoire; family usage can be found in (Bennett et al., 2008; Harp et al., 2007); CIS429 was a 62 y.o. male first presenting with optic neuritis and the repertoire had 2% VH1 usage, 0% VH2, 77% VH3, and 19% VH4.
Bias was considered significantly different from random frequency (Cook and Tomlinson, 1995) or expected frequency in HCPB (Brezinschek et al., 1997; Brezinschek et al., 1998; Dorner et al., 1997; Dorner et al., 1998a; Dorner et al., 1998b; Dorner et al., 1998c; Farner et al., 1999; Hansen et al., 2000; Monson et al., 2000). VH2 bias was also observed in CD19 repertoires from ON4–7, and CD138 repertoires from ON3-3, ON3–5 and ON4–7.
Signature score was calculated as outlined in materials and methods, and uses both CD19 and CD138 sequences. The average score among MS patients is 10.9 ±2.0.
months from first demyelinating event to MS diagnosis.
One spinal cord lesion was observed by T2 weighted MRI