Supplementary Material
Higher frequencies of HLA DQB1*05:01 and anti-glycosphingolipid antibodies in a cluster of severe Guillain-Barré syndrome
L. Schirmer, MD1, V. Worthington, PhD2, U. Solloch, PhD3, V. Loleit, MD1, V. Grummel1, N. Lakdawala, MSc2, D. Grant, MSc2, R. Wassmuth, MD4,5, A. H. Schmidt, MD, PhD3,4, F. Gebhardt, MD6, T. F. M. Andlauer PhD7,8, J. Sauter, PhD3, A. Berthele, MD1, M. P. Lunn, MD2, B. Hemmer, MD1,8
1 Department of Neurology, Klinikum rechts der Isar, Technical University of Munich, Munich, Germany
2MRC Centre for Neuromuscular Diseases & Neuroimmunology and CSF Laboratory, National Hospital for Neurology, London, United Kingdom
3DKMS German Bone Marrow Center, Tübingen, Germany
4 DKMS Life Science Lab, Dresden, Germany
5 Department of Quality Management, University Hospital Düsseldorf, Düsseldorf, Germany
6 Institute for Medical Microbiology, Klinikum rechts der Isar, Technical University of Munich, Munich, Germany
7 Max Planck Institute of Psychiatry, Munich, Germany
8 Munich Cluster for Systems Neurology (SyNergy), Munich, Germany
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Supplementary table 1Detailed clinical, electrophysiological and CSF characteristics in GBS patients
Cluster GBS # / Age / Sex / NadirF Score (1-5) / Clinical follow-up (months) / Follow-up
F Score
(1-5) / Cranial nerve involvement / Sensory deficits / Preceding vaccinations/
infections / Electro-physiological classification / CSF leukocyte count (x109/L) / CSF/serum albumin ratio (x10-3) / Oligoclonal bands (OCB)
1 / 70 / m / 4 / n/a / n/a / y / y / n / demyelinating / n/a / n/a / n/a
2 / 45 / f / 1 / 2 / 1 / n / y / gastroenteritis / n/a / 12 / 6.4 / polyclonal
3 / 57 / f / 5 / 5 / 2 / y / y / gastroenteritis / equivocal / 2 / 5.6 / polyclonal
4 / 19 / f / 5 / 70 / 2 / y / y / respiratory infection / equivocal / 0 / 5 / polyclonal
5 / 54 / m / 2 / 69 / 0 / n / n / influenza vaccination, respiratory infection / demyelinating / 8 / 5 / polyclonal
6 / 68 / m / 4 / 69 / 2 / n / n / respiratory infection / demyelinating / 2 / 12.4 / identical
7 / 31 / m / 2 / n/a / n/a / y / n / respiratory infection / demyelinating / 3 / 6 / polyclonal
8 / 42 / m / 2 / 69 / 0 / y / y / n / demyelinating / 1 / 6.6 / polyclonal
9 / 51 / f / 4 / 14 / 1 / y / n / gastroenteritis / equivocal / 15 / 7.9 / polyclonal
10 / 36 / f / 3 / n/a / n/a / n / n / n / demyelinating / 2 / 7.2 / identical
11 / 16 / m / 2 / 67 / 1 / y / y / respiratory infection / demyelinating / 0 / 16.3 / polyclonal
12 / 44 / m / 4 / CIDP / - / y / y / n / demyelinating / 0 / 7.9 / polyclonal
13 / 67 / m / 5 / 66 / 1 / y / y / gastroenteritis / demyelinating / 10 / 17.9 / identical
14 / 37 / m / 5 / n/a / n/a / n / y / respiratory infection / demyelinating / 3 / 10.7 / polyclonal
Sporadic GBS #
1 / 55 / m / 2 / 86 / 0 / n / n / gastroenteritis / demyelinating / 5 / 7.6 / n/a
2 / 57 / m / 4 / 4 / 2 / y / n / n / equivocal / 2 / 8.4 / polyclonal
3 / 33 / m / 2 / n/a / n/a / y / y / n / demyelinating / 1 / 5.9 / polyclonal
4 / 85 / m / 1 / 2 / 1 / y / y / gastroenteritis / demyelinating / 2 / 17.6 / polyclonal
5 / 71 / m / 2 / CIDP / - / n / y / tetanus/diphteria/
typhus vaccination / demyelinating / n/a / n/a / n/a
6 / 49 / m / 4 / 57 / 2 / n / n / urinary infection / demyelinating / 0 / 6 / polyclonal
7 / 69 / m / 3 / 2 / 1 / n / y / respiratory infection / demyelinating / 10 / 12.7 / OCB
8 / 71 / m / 2 / 10 / 1 / n / y / gastroenteritis / demyelinating / 0 / 9.5 / identical
9 / 53 / f / 4 / 62 / 2 / y / n / respiratory infection / demyelinating / 1 / 9.9 / identical
10 / 43 / m / 4 / CIDP / - / y / n / gastroenteritis / demyelinating / 10 / 13.3 / polyclonal
11 / 63 / f / 4 / 55 / 1 / y / y / tetanus vaccination / demyelinating / 8 / 32.5 / identical
12 / 53 / m / 5 / 54 / 1 / y / y / gastroenteritis / equivocal / 1 / 11.6 / polyclonal
13 / 21 / m / 2 / 31 / 0 / n / y / gastroenteritis / equivocal / 5 / 6.3 / polyclonal
14 / 55 / f / 2 / 57 / 0 / y / y / influenza vaccination, respiratory infection / normal / 2 / 6.5 / polyclonal
15 / 56 / m / 4 / 53 / 1 / n / y / n / demyelinating / 1 / 24.4 / identical
16 / 33 / m / 2 / 51 / 1 / n / n / n / demyelinating / 4 / 21.4 / polyclonal
17 / 56 / f / 4 / CIDP / - / n / y / n / demyelinating / 5 / n/a / n/a
18 / 45 / f / 1 / 14 / 1 / n / y / n / demyelinating / 4 / n/a / n/a
19 / 83 / f / 3 / 19 / 0 / y / y / n / normal / 1 / 6.8 / polyclonal
20 / 53 / m / 4 / 48 / 2 / y / y / gastroenteritis / demyelinating / 6 / 12.9 / polyclonal
21 / 65 / m / 4 / n/a / n/a / n / y / respiratory infection / demyelinating / n/a / n/a / n/a
22 / 63 / m / 2 / 47 / 2 / y / y / n / demyelinating / n/a / n/a / n/a
23 / 64 / m / 2 / died / - / n / n / respiratory infection / demyelinating / 1 / 7.1 / polyclonal
24 / 77 / m / 4 / died / - / n / y / n / demyelinating / 1 / 16.6 / identical
25 / 66 / m / 4 / died / - / n / y / gastroenteritis / demyelinating / n/a / n/a / n/a
26 / 29 / m / 1 / 33 / 0 / y / y / n / equivocal / 2 / 33.5 / polyclonal
Legend:f = female, m = male; n = no; y = yes; OCB = oligoclonal bands in CSF; identical = identical bands in both serum and CSF; CIDP = chronic inflammatory demyelinating polyneuropathy;n/a = not available.
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Supplementary table 2Anti-Cj and glycosphingolipidantibody reactivities and HLA class II typing in GBS patients
Cluster GBS # / Cj serology (IgG; IgA) / Anti- glycosphingolipid antibodies(IgG; IgM) / HLA class II alleles
DRB1 / DQB1 / DPB1
1 / n/a / n/a / n/a / n/a / n/a / n/a / n/a / n/a
2 / IgG / neg / 13:02:01 / 11:01:01 / 03:01:01 / 06:04:01 / 04:01:01 / 02:01:02
3 / IgG / Sulfatide
(1:160000; 1:1000) / 01:01:01 / 11:01:01 / 05:01:01 / 03:01:01 / 04:01:01 / 04:01:01
4 / neg / GM1 (1:1500; neg), GD1b (1:450; neg) / 11:01:01 / 07:01:01G / 03:01:01 / 02:02:01 / 04:01:01 / 04:01:01
5 / neg / neg / 04:04:01 / 07:01:01G / 03:02:01 / 02:02:01 / 04:01:01G / 04:02:01G
6 / neg / GM1 (1:3000; neg) / 04:01:01 / 04:01:01 / 03:01:01 / 03:02:01 / 04:01:01 / 03:FNVX
7 / IgG / neg / 03:01:01 / 13:01:01 / 02:01:01 / 06:03:01 / 19:01 / 02:01:02
8 / IgG / GQ1b (borderline) / 01:01:01 / 15:01:01 / 05:01:01 / 06:02:01 / 04:01:01 / 03:FNVX
9 / IgG / GQ1b (borderline) / 01:01:01 / 07:01:01G / 05:01:01 / 03:03:02 / 04:01:01 / 03:FNVX
10 / IgG / neg / 15:01:01 / 13:02:01 / 06:HTC / 06:FTZK / 04:01:01G / 04:02:01G
11 / IgG / GalC (borderline) / 11:01:01 / 03:01:01 / 03:01:01 / 02:01:01 / 04:02:01 / 04:02:01
12 / IgG / Sulfatide
(1:8000; 1:5000) / 01:02:01 / 04:01:01 / 05:01:01 / 03:02:01 / 04:01:01G / 04:02:01G
13 / neg / neg / 01:01:01 / 16:01:01 / 05:01:01 / 05:02:01 / 10:01 / 03:FNVX
14 / IgG / neg / 01:01:01 / 16:01:01 / 05:01:01 / 05:02:01 / 04:01:01G / 04:02:01G
Sporadic GBS #
1 / IgG, IgA / neg / 04:04:01 / 09:01:02 / 03:02:01 / 03:03:02 / 06:01 / 04:02:01
2 / IgG / n/a / n/a / n/a / n/a / n/a / n/a / n/a
3 / IgG / GM1 (1:2000; neg) / n/a / n/a / n/a / n/a / n/a / n/a
4 / neg / neg / 15:01:01 / 15:01:01 / 06:02:01 / 06:02:01 / 04:01:01 / 04:01:01
5 / neg / neg / n/a / n/a / n/a / n/a / n/a / n/a
6 / neg / n/a / 11:01:01 / 07:01:01G / 03:01:01 / 02:02:01 / 04:01:01 / 03:FNVX
7 / neg / neg / 01:01:01 / 11:01:01 / 05:01:01 / 03:01:01 / 04:01:01G / 04:02:01G
8 / neg / GM1
(1:4000; 1:1500) / 15:01:01 / 03:01:01 / 02:01:01 / 06:02:01 / 13:FNVU / 04:01:01
9 / IgG / neg / 11:01:01 / 07:01:01G / 03:01:01 / 03:03:02 / 14:01:01 / 04:01
10 / neg / neg / 13:02:01 / 13:01:01 / 06:HTC / 06:MDH / 03:FNVX / 03:FNVX
11 / neg / neg / 12:JV / 04:01:01 / 03:01:01 / 03:02:01 / 04:01:01 / 04:01:01
12 / IgG, IgA / neg / 13:01:01 / 15:01:01 / 06:02:01 / 06:03:01 / 04:01:01 / 19:01
13 / n/a / neg / n/a / n/a / n/a / n/a / n/a / n/a
14 / IgG / neg / n/a / n/a / n/a / n/a / n/a / n/a
15 / neg / neg / 08:03:02 / 13:02:01 / 03:01:01 / 06:04:01 / 04:02:01 / 02:01:02
16 / IgG / neg / n/a / n/a / n/a / n/a / n/a / n/a
17 / n/a / neg / n/a / n/a / n/a / n/a / n/a / n/a
18 / neg / neg / n/a / n/a / n/a / n/a / n/a / n/a
19 / IgG / GT1a
(1:16000; neg) / 15:01:01 / 07:01:01G / 02:02:01 / 06:02:01 / 17:01 / 02:01:02
20 / IgG / neg / 03:01:01 / 07:01:01G / 02:01:01 / 02:02:01 / 10:01 / 01:01:01
21 / IgG / neg / 11:01:01 / 07:01:01G / 03:01:01 / 02:02:01 / 03:FNVX / 02:01:02
22 / neg / neg / 04:01:01 / 07:01:01G / 03:02:01 / 02:02:01 / 04:01:01 / 01:01:01
23 / neg / neg / 08:01:01G / 03:01:01 / 02:01:01 / 04:02:01 / 04:01:01 / 02:01:02
24 / neg / neg / 12:JV / 03:01:01 / 03:01:01 / 02:01:01 / 19:01 / 02:01:02
25 / IgG, IgA / neg / n/a / n/a / n/a / n/a / n/a / n/a
26 / neg / neg / n/a / n/a / n/a / n/a / n/a / n/a
Legend:Cj: Campylobacter jejuni; n/a = not available; neg = negative; if applicable, borderline and anti-ganglioside/sulfatide IgG and IgM titers are shown in brackets; HLA alleles with identical nucleotide sequences for the peptide binding domain (exon 2) were grouped and designated by an upper case ‘G’ which follows the first 3 fields of the allele designation of the lowest numbered allele in the group; where a better typing resolution could be reached, generic codes for multiple allele designations (e.g., FNVX or HTC) were used.
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Supplementary table 3HLA II allele frequencies for the loci DRB1, DPB1 and DQB1 in cluster (n=13) and sporadic (n=16)GBS patients and control subjects (n=12602).
Allele / Cluster GBS / Sporadic GBS / ControlDRB1*15:01 / 0.076923 / 0.156250 / 0.140796
DRB1*07:01g / 0.115385 / 0.187500 / 0.130279
DRB1*01:01g / 0.192308 / 0.031250 / 0.094554
DRB1*03:01 / 0.076923 / 0.125000 / 0.094386
DRB1*13:01g / 0.038462 / 0.062500 / 0.075389
DRB1*04:01 / 0.115385 / 0.062500 / 0.074846
DRB1*11:01g / 0.153846 / 0.125000 / 0.074810
DRB1*13:02 / 0.076923 / 0.062500 / 0.042219
DRB1*08:01 / 0.000000 / 0.031250 / 0.028678
DRB1*04:04 / 0.038462 / 0.031250 / 0.026136
DRB1*16:01 / 0.076923 / 0.000000 / 0.019476
DRB1*12:01g / 0.000000 / 0.062500 / 0.017556
DRB1*01:02 / 0.038462 / 0.000000 / 0.012552
DRB1*09:01g / 0.000000 / 0.031250 / 0.008858
DRB1*08:03 / 0.000000 / 0.031250 / 0.002026
DPB1*04:01g / 0.461538 / 0.343750 / 0.420643
DPB1*02:01g / 0076923 / 0.156250 / 0.149684
DPB1*04:02g / 0.230769 / 0.093750 / 0.116628
DPB1*03:01g / 0.153846 / 0.125000 / 0.110779
DPB1*01:01g / 0.000000 / 0.062500 / 0.043644
DPB1*13:01g / 0.000000 / 0.031250 / 0.018053
DPB1*17:01g / 0.000000 / 0.031250 / 0.015712
DPB1*14:01 / 0.000000 / 0.031250 / 0.014869
DPB1*10:01 / 0.038462 / 0.031250 / 0.014452
DPB1*06:01 / 0.000000 / 0.031250 / 0.012875
DPB1*19:01g / 0.038462 / 0.062500 / 0.008848
DQB1*02:01g / 0.153846 / 0.281250 / 0.193686
DQB1*03:01g / 0.192308 / 0.218750 / 0.193640
DQB1*06:02g / 0.076923 / 0.156250 / 0.132934
DQB1*05:01g / 0.230769 / 0.031250 / 0.117960
DQB1*03:02g / 0.115385 / 0.093750 / 0.088857
DQB1*06:03g / 0.038462 / 0.062500 / 0.080021
DQB1*03:03g / 0.038462 / 0.062500 / 0.043753
DQB1*06:04g / 0.076923 / 0.062500 / 0.035798
DQB1*04:02g / 0.000000 / 0.031250 / 0.031941
DQB1*05:02g / 0.076923 / 0.000000 / 0.024380
Legend: Note DRB1*01:01 and DQB1*05:01 allele frequencies are highlighted and shown in italic letters; alleles differing only by synonymous mutations or mutations outside exon 2 (peptide binding domain) were grouped and marked with ‘g’ as described before29.
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