Anti-SOX1 Antibodies in Paraneoplastic Neurological Syndrome

Abstract

Anti-Sry-like high mobility group box (SOX) 1 antibodies (abs) are partly characterized onconeural autoantibodies (autoabs) due to their correlation with neoplastic diseases. Anti-SOX1 abs are associated with various clinical manifestations, including Lambert-Eaton myasthenic syndrome (LEMS) and paraneoplastic cerebellar degeneration (PCD). However, the clinical characteristics of patients with anti-SOX1 abs have not been described in detail. This review systematically explores the reported patients with anti-SOX1 abs and analyzes these cases for demographic characteristics, clinical features, coexisting neuronal autoabs, neuroimaging findings, treatment, and clinical outcomes. In addition, considering that PCD is the most common paraneoplastic neurological syndrome and that the association between PCD and anti-SOX1 abs remains unclear, we focus on the presence of autoabs in relation to PCD and associated tumors. PCD-associated autoabs include various intracellular autoabs (e.g., anti-Hu, anti-Yo, anti-Ri, and anti-SOX1) and cell-surface autoabs (anti-P/Q-type voltage-gated calcium channel). Commonly involved tumors in PCD are small-cell lung cancer (SCLC), gynecological, and breast tumors. LEMS is the most common clinical symptom in patients with anti-SOX1 abs, followed by PCD, and multiple neuronal autoabs coexist in 47.1% of these patients. SCLC is still the predominant tumor in patients with anti-SOX1 abs, while non-SCLC is uncommon. No consistent imaging feature is found in patients with anti-SOX1 abs, and there is no consensus on either the therapy choice or therapeutic efficacy. In conclusion, the presence of anti-SOX1 abs alone is a potential predictor of an uncommon paraneoplastic neurological disorder, usually occurring in the setting of LEMS, PCD, and SCLC. The detection of anti-SOX1 abs contributes to an early diagnosis of underlying tumors, given the diversity of clinical symptoms and the absence of characteristic neuroimaging features.

Paraneoplastic myelitis associated with durvalumab treatment for extensive-stage small cell lung cancer

“…In a series of 468 patients with and without PNS, 61 were ZIC-4 positive, including 92% of SCLC [ 18 ]. SOX1 antibodies are found in 64% of patients with Lambert-Eaton Myasthenic Syndrome(LEMS) in association with voltage-gated calcium channel antibodies as serological markers of SCLC [ 19 ]. They are also identified in 40% of patient with SCLC without neurological syndrome [ 19 ].…”

“…SOX1 antibodies are found in 64% of patients with Lambert-Eaton Myasthenic Syndrome(LEMS) in association with voltage-gated calcium channel antibodies as serological markers of SCLC [ 19 ]. They are also identified in 40% of patient with SCLC without neurological syndrome [ 19 ]. This patient was both ZIV-4 and SOX1 positive after receiving ICIs therapy, indicating neurological irAEs caused by durvalumab therapy were associated with PNS..…”

Neuropsychiatric Disorders Due to Limbic Encephalitis: Immunologic Aspect

“…LE is a rare neurologic presentation in this entity. Onconeural antibodies associated with paraneoplastic LE are Ma, Hu, Ri, CRMP5, and SOX1 [ 66 , 145 ], with Ma2 being the major intracellular antibody causing paraneoplastic LE [ 146 ]. In paraneoplastic LE associated with lung cancer, Hu and cell surface GABA-BR antibodies were the most frequently encountered antibodies, whereas in paraneoplastic LE associated with testicular tumor, Ma2 antibody is the most frequent antibody [ 147 , 148 ].…”

Simultaneous paraneoplastic cerebellar degeneration, Lambert-Eaton syndrome and neuropathy associated with AGNA/anti-SOX1 and VGCC antibodies

“…Almost 20% of patients with SOX1-antibodies suffer from PCD, and about 8% develop axonal neuropathy [ 3 ]. While the cerebellar degeneration of our patient can be attributed to PCD, the cause of neuropathy may not be conclusively solved.…”

“…Cisplatin is known to lead to sensory neuropathy; however, an axonal motor neuropathy without the involvement of sensory fibres would be unlikely. Yet, SOX1 antibodies are associated with an axonal neuropathy that may affect motoric nerves [ 3 , 4 ]. Further investigations revealed no other apparent cause of neuropathy.…”