Table 2.
HLA studies in neuromyelitis optica (SSP-PCR, sequence-specific primers–polymerase chain reaction; PCR-SSO, polymerase chain reaction–sequence specific oligoprobes; SBT, sequencing-based typing; MOG-Ab, myelin oligodendrocyte glycoprotein antibody).
| HLA regions | Number of samples | Population | Source of sample/assay methods | Associations | Year | Ref |
|---|---|---|---|---|---|---|
| HLA-A, B, C HLA-DRB1, DQB1, DPB1 |
15 NMO patients and 606 healthy controls | Southern Brazilian | Peripheral blood/Sanger sequencing | There was significant association between HLA-DRB1*16:02, *04:05, C*15:02 alleles and NMO susceptibility. | 2019 | (22) |
| HLA-DRB1, DQB1 | 42 NMO patients and 150 healthy controls | French Afro-Caribbean | Peripheral blood/PCR-SSO | There was significant association between HLA-DRB1*03 alleles and NMO disease. | 2010 | (23) |
| HLA-DRB1, 3, 4 and 5 | 27 NMOSD patients and 28 healthy controls | Mulatto Brazilian (Ribeira˜o Preto) | Peripheral blood/PCR-SSP | HLA-DRB1*03 and DRB1*10 alleles were overrepresented in NMOSD patients compared to controls. | 2009 | (24) |
| HLA-DRB1 | 35 NMO patients and 99 healthy controls | Brazilian (Mexico City) | Peripheral blood/PCR-SSP | HLA-DRB1*03 and DRB1*10 alleles were more common in NMO cases compared to controls. | 2016 | (25) |
| HLA-DRB1, DQA1 and DQB1 | 65 NMO patients and 100 healthy controls | Brazilian (Rio de Janeiro) | Peripheral blood/PCR-SSO and SSP | HLA-DRB1*01:02, 03:01, DQB1*02:01 and DQA1*01:05 alleles were more common in NMO cases compared to controls. DRB1*03:01- DQA1*05:01/3/5-DQB1*02:01, DRB1*01:02-DQA1*01:01-DQB1*05:01 and DRB1*10:01-DQA1*01:04/5-DQB1*05:01 haplotypes were associated with NMO. |
2017 | (26) |
| HLA-A, B, C, DRB1 and DQB1 | 71 NMO patients and 97 healthy controls | Mexican | Peripheral blood/SBT | Risk HLA alleles for NMO: DQB1*03:01, DRB1*08:02, DRB1*16:02, DRB1*14:06, DQB1*04:02, B*35:14, B*39:06 and protective alleles include: DQB1*03:02, DQB1*02:02, DRB1*04:07, DRB1*07:01 and B*39:05 | 2020 | (28) |
| HLA-A, B, DQA1, DQB1, DRB1, and DPB1 | 39 NMO, 6 patients at risk of NMO, and 100 healthy controls | French Caucasian | Peripheral blood/PCR-RFLP and PCR-SSP | HLA-DQA1*102, * 501, DQB1*0201 DRB1*03 alleles were significantly associated with NMO. There was no correlation between distribution of HLA alleles and IgG antibody subgroups |
2009 | (29) |
| HLA-DRB1 | 22 NMO patients and 225 healthy controls | Spanish Caucasian | Peripheral blood | HLA-DRB1*10 allele was significantly associated with NMO disease. | 2011 | (30) |
| HLA-A, B, C, DRA, DRB1, DQA1, DQB1, DPA1, DPB1, E, F, G, DOA, DOB, DMA, and DMB | 31 NMOSD patients and 429 healthy controls | Japanese | Peripheral blood/NGS-based HLA genotyping | HLA-DQA1*05:03 allele had the most association with NMOSD. | 2019 | (31) |
| HLA-DRB1 and DPB1 | 77 NMO, 39 NMOSD patients and 367 healthy controls | Japanese | Peripheral blood/PCR-SSO | Higher occurrence of HLA-DRB1*1602, DPB1*0501 and lower occurrence of DRB1*0901 alleles were associated with anti-AQP4 antibody positive patients. | 2012 | (32) |
| HLA-DRB1 and DPB1 | 165 NMOSD patients | Japanese | Peripheral blood/SSO (Luminex) | HLA-DRB1*08:02 and DPB1*05:01 alleles were associated with disease and DRB1*09:01 was protective allele in NMOSD. | 2021 | (33) |
| HLA-DRB1 and DPB1 | 184 NMOSD patients and 317 healthy controls | Japanese | Peripheral blood/PCR- SSO | HLA-DRB1*08:02, -DRB1*16:02 alleles were associated to NMO whereas DRB1*09:01 allele was protective factor. | 2020 | (27) |
| HLA-DRB1 and DPB1 | 38 NMOSD AQP4-Ab+ patients and 125 healthy controls | Japanese | Peripheral blood/PCR-SSO | HLA-DPB1*0501 allele was associated with NMOSD and reinforced presence of anti AQP4-Ab | 2008 | (34) |
| HLA-DRB1 | 61 NMO and 32 NMOSD patients and 300 healthy controls | Indian | Peripheral blood/PCR-SSP | HLA-DRB1*03 allele was significantly associated with disease and persist associated with anti-AQP4 subtype. HLA-DRB1*10 allele was trended to associated with disease. |
2015 | (35) |
| HLA-DP | 86 NMOSD patients and 29 healthy controls | Chinese | Peripheral blood/flow cytometry and real-time PCR | HLA-DPB1*0501 allele was associated with NMOSD through affect transcription levels of HLA-DP gene in antigen presenting cells. | 2019 | (36) |
| HLA-DQA1, DQB1 and DRB1 | 41 NMO patients and 200 healthy controls | Caucasian (Danish) | Peripheral blood/PCR-SSO | HLA-DQB1*0402 allele was significantly associated with NMO disease. There were no significant differences in HLA distributions between anti-AQP4 subtypes. | 2011 | (37) |
| HLA-DQ and DR | 8 NMOSD patients with AQP4-Ab, 10 with MOG-Ab and 14 healthy controls | Swiss | Peripheral blood/PCR-SSP | HLA DQB1∗02, DRB1∗01 and DRB1∗03 alleles were significantly associated with AQP4-Ab+patients. | 2020 | (38) |
| HLA-A, B, C, DQA1, DQB1, DRB1 and DPB1 | 5 NMO patients | Southern Finnish | Peripheral blood/NGS and SSP | HLA-DPB1*0501 allele was associated with AQP4-Ab+ NMO patient. | 2015 | (39) |
| HLA-A, -B, -Cw, DRB1, DQB1 and DRB3/4/5 | 85 patients (include 43 MOG-IgG and 42 AQP4-IgG seropositive) and 5,604 healthy controls | Dutch | Peripheral blood/SSO (Luminex) and PCR-SSO | HLA-A*01, B*08, and -DRB1*03 alleles were significantly associated with AQP4-IgG NMOSD. There was no association of MOG-IgG cases with HLA alleles. | 2020 | (40) |
| HLA-DRB1 and DQB1 | 35 NMO patients and 74 healthy controls | Israeli Muslim | Peripheral blood/PCR-SSO, Luminex technology and PCR-SSP | There was a significant positive association of HLA-DRB1*04:04 and DRB1*10:01 alleles and negative association of HLA-DRB1*07 and DQB1*02:02 alleles with NMO. | 2016 | (41) |
| HLA-DRB1 and DPB1 | 30 NMO patients and 93 controls | Southern Han Chinese | Peripheral blood/SBT | The frequency of HLA-DRB1*1602 and DPB1*0501 alleles was significantly higher in NMO AQP4-Ab-positive patients. DRB1*0901 allele had lower frequency in disease. | 2010 | (42) |