Electrodiagnostic findings related to anti-GM1 and anti-GQ1b antibodies in Guillain-Barré syndrome

Antibodies against the gangliosides GM1 and GQ1b may induce conduction failure in mice. To investigate their possible site of action in the Guillain-Barré syndrome (GBS), we studied the relation between serum anti-GM1 and anti-GQ1b antibodies and electromyography in 124 GBS patients. Anti-GM1 antibodies were found in 22 (18%) and anti-GQ1b antibodies in 5 (4%) patients. Anti-GM1 antibodies were associated with low distal compound muscle action potential amplitudes and relatively high compound sensory nerve action potential (CSNAP) amplitudes. In none of the patients with anti-GQ1b antibodies could CSNAPs be detected. Patients with anti-GM1 and anti-GQ1b antibodies were heterogenous with respect to electrodiagnostic features exclusive for demyelination or axonal degeneration, although the anti-GM1 positive patients tended to have more axonal degeneration. In conclusion, electromyographic studies indicate selective and more severe damage of motor nerves in patients with anti-GM1 antibodies, while patients with anti-GQ1b antibodies have more severe damage of sensory nerves. These antibodies may interfere with the electrophysiologic properties of different nerve fibers and thereby contribute to the clinical heterogeneity in GBS. © 1997 John Wiley & Sons, Inc. Muscle Nerve, 20: 446–452, 1997     

Cerebrospinal fluid antibodies to tubulin are elevated in the patients with multiple sclerosis

Background and purpose: The aim of this study was to compare the levels of anti‐tubulin antibodies (anti‐TU) in cerebrospinal fluid (CSF) and serum using bovine tubulin as the antigen in one enzyme‐linked immunosorbent assay (ELISA) method (anti‐TUb antibodies) and a synthetic neuron‐specific octapeptide of tubulin in a second ELISA method (anti‐TUs antibodies). Methods: Paired CSF and serum samples were obtained from 34 multiple sclerosis (MS) patients, 13 patients with various other neurological diseases (control diseases) and 17 normal control patients (CN). Results: CSF levels of anti‐TUs and anti‐TUb antibodies were significantly lower in the CN group when compared to those in the MS group. On the contrary, serum levels of anti‐TU antibodies did not differ among groups. The intrathecal synthesis of anti‐TUs antibodies in comparison with anti‐TUb was significantly increased in all groups. Significant correlations between anti‐TUb and anti‐TUs antibodies were observed in the CSF of all three groups. However, with regard to serum, a similar relationship was only found in the MS group. Conclusions: The estimation of anti‐TU in CSF can contribute to the overall assessment of axonal damage; on the contrary serum anti‐tubulin antibodies were not useful for differential purposes in MS. The antibodies to the neuron‐specific portion of tubulin seemed to be synthesised predominantly intrathecally.     

Miastenia gravis ocular y factores asociados al desarrollo de una generalización secundaria: descripción de una serie española

IntroductionOcular myasthenia gravis (MG) is the most common phenotype of MG at onset. A variable percentage of these patients develop secondary generalisation; the risk factors for conversion and the protective effect of immunosuppressive treatment are currently controversial.Patients and methodsWe designed a retrospective single-centre study with the aim of describing the demographic, clinical, and laboratory characteristics of a Spanish cohort of patients with ocular MG from Hospital Universitario de Albacete from January 2008 to February 2020.ResultsWe selected 62 patients with ocular MG from a cohort of 91 patients with MG (68.1%). Median age at diagnosis was 68 (IQR, 52-75.3), and men accounted for 61.3% of the sample (n = 38). Most patients presented very late-onset ocular MG (n = 34, 54.8%). Binocular diplopia was the most frequent initial symptom (51.7%). The rate of progression to generalised MG was 50% (n = 31), with a median time of 6 months (IQR, 2-12.8). Female sex (OR: 5.46; 95% CI, 1.16-25-74; p = .03) and anti–acetylcholine receptor antibodies (OR: 8.86; 95% CI, 1.15-68.41; p = .04) were significantly associated with the risk of developing generalised MG.ConclusionsThe conversion rate observed in our series is relatively high. Generalisation of MG mainly occurs during the first 2 years of progression, and is strongly associated with female sex and especially with the presence of anti–acetylcholine receptor antibodies.     

Anti‐ganglioside autoantibodies in type 1 diabetes

Type 1 diabetes is an autoimmune disease that is accompanied by an immune response against pancreatic cells. As gangliosides are expressed in both peripheral nerves and pancreatic cells, we examined the possibility of correlation between type 1 diabetes, anti‐ganglioside autoantibodies, and neuropathy. Fifty diabetic patients and 30 controls with other autoimmune diseases underwent neurological examination and search for antibodies to gangliosides, glutamic acid decarboxylase (GAD₆₅), and tyrosine phosphatase (IA2). Sixteen (32%) diabetic patients had neuropathy. Twelve diabetic sera were found to have anti‐ganglioside autoantibodies. Twenty sera were positive for anti‐GAD₆₅ and nine for anti‐IA2 antibody. Sera from three control patients had anti‐ganglioside autoantibodies. No significant correlation was found between autoantibodies, neuropathy, and disease duration. Disease duration was shorter in patients with antibodies to GAD₆₅ and IA2 and longer in neuropathic patients. The higher prevalence of antibodies in diabetic patients compared to controls may reflect the common pattern of antigens shared by peripheral nerve and pancreatic islet cells. Muscle Nerve, 2009     

Immunochemical and clinical effects of immunosuppressive treatment in monoclonal IgM neuropathy.

A pathogenic role of the M protein in monoclonal IgM neuropathy has been suggested. This is based among other things on a close relation between immunosuppressive treatment, lowered concentration of M protein, and clinical effect. We studied five patients with monoclonal IgM and antibodies to peripheral nerve myelin. The immunosuppressive treatment was beneficial in three of the patients. In three patients there was a relationship between antibody concentration and clinical effect (in one there was no change in antibody concentrations and correspondingly no change in clinical status, and in two patients clinical improvement corresponded to decreased antibody concentrations). In two patients, however, there was no clear correlation, since one patient improved despite increasing antibody concentrations and one patient did not improve despite a lowered antibody concentration. It is therefore possible that other mechanisms may contribute to the effect of treatment.     

Cerebrospinal fluid and serum antibodies against neurofilaments in patients with amyotrophic lateral sclerosis

Background: The aim of the study was to assess autoimmune involvement in amyotrophic lateral sclerosis (ALS). Methods: We measured IgG antibodies against light (NFL) and medium (NFM) subunits of neurofilaments using ELISA in paired cerebrospinal fluid (CSF) and serum samples from 38 ALS patients and 20 controls. Results: Serum levels of anti‐NFL were higher in ALS patients than in controls (P < 0.005). Serum anti‐NFL antibodies and intrathecal anti‐NFM antibodies were related to patient disability (serum anti‐NFL: P < 0.05; intrathecal anti‐NFM: P < 0.05). Anti‐NFL levels were significantly correlated with anti‐NFM levels in ALS (P < 0.001) and the control group (P < 0.0001) in the CSF, but not in serum. Anti‐NFL and anti‐NFM antibodies significantly correlated between serum and CSF in the ALS group (anti‐NFL: P < 0.0001; anti‐NFM: P < 0.001) and in the control group (anti‐NFL: P < 0.05; anti‐NFM: P < 0.05). Conclusions: Autoimmune humoral response to neurocytoskeletal proteins is associated with ALS.     

SOX1 antibodies in sera from patients with paraneoplastic neurological syndromes

Objectives – SOX1 antibodies have been described in patients with Lambert–Eaton myasthenic syndrome (LEMS) in association with voltage‐gated calcium channel antibodies as serological markers of small cell lung cancer (SCLC). This study was aimed to screen for additional SOX1 autoimmunity in onconeural antibody‐positive sera from patients with paraneoplastic neurological syndromes (PNS) other than LEMS and to identify the clinical–immunological profile and associated tumours of patients with coexisting SOX1 antibodies. Methods– We retrospectively analysed sera from 55 patients with different PNS positive for well‐characterized antineuronal antibodies for the presence of SOX1 antibodies by recombinant ELISA and immunoblot. Results– Eight (14.5%) patients showed additional SOX1 antibodies in the ELISA and the recombinant immunoblot. Five patients had coexisting Hu antibodies, while the other three showed coexisting CV2/CRMP5, amphiphysin, and coexisting CV2/CRMP5 and Hu antibodies, respectively. PNS included (partially overlapping) subacute sensory neuropathy, subacute sensorimotor neuropathy, cerebellar degeneration, brainstem encephalitis, encephalomyelitis and limbic encephalitis. No tumour was detected in two patients, while the others had lung cancer (four SCLC and two non‐SCLC). One patient showed SOX1‐specific intrathecal antibody synthesis. Conclusions– We describe SOX1 reactivity for the first time overlapping with CV2/CRMP5 and amphiphysin antibodies. SOX1 reactivity is predominantly associated with Hu antibodies and SCLC, but can occur also in other types of lung cancer. Neurological manifestations present in patients with coexisting SOX1 antibodies and well‐characterized antineuronal antibodies do not differ from those previously described in patients positive for antineuronal antibodies but no SOX1‐specific anti‐glial antibodies.     

IL-8单抗对颅脑损伤后继发性脑损害的保护作用

目的　观察抗IL 8单抗对兔脑损伤后脑内炎症反应的抑制作用 ,以及对血脑屏障通透性和创伤性脑水肿的影响 ,探讨颅脑损伤后继发性脑损害新的治疗方法。方法　采用自由落体兔脑损伤模型 ,观察家兔抗IL 8单抗治疗前后脑组织中IL 8表达、中性粒细胞 (PMNL)浸润有无变化 ,同时检测脑组织含水量的变化 ,并用胶体金示踪 ,电镜观察抗IL 8单抗使用前后血脑屏障通透性有无改善。结果　抗IL 8单抗治疗组与对照组相比 ,伤后脑组织中IL 8无表达 ,PMNL浸润也明显减少 (P <0 .0 1 ) ,血脑屏障通透性降低 ,脑含水量下降 (P <0 .0 5)。结论　颅脑损伤后早期给予抗IL 8单抗治疗 ,可抑制IL 8的表达 ,抑制IL 8趋化PMNL的作用 ,减少组织中PMNL的浸润 ,减轻脑损伤后脑内炎症反应 ,降低血脑屏障通透性 ,减轻创伤性脑水肿 ,从而改善继发性脑损害。     

Effect of thymectomy and immunosuppressive therapy on anti-neuroblastoma antibody levels in patients with myasthenia gravis

Antibodies reacting with human neuroblastoma cells (NBL) are distinct from the "classical" anti-acetylcholine receptor (AChR) antibodies in myasthenia gravis (MG). The influence of therapeutic interventions on serum anti-NBL antibody levels was followed in 42 MG patients. Thymectomy alone was performed in 28 patients while immunosuppressive medication was given to 14 patients out of whom 10 also had a thymectomy. In most patients serum anti-NBL antibody titers declined after thymectomy and/or during immunosuppressive treatment, though individual variations in the antibody response could be observed. Sequential examinations of individual patients revealed an association between the clinical severity of MG and anti-NBL antibody levels. No correlation between the treatment-induced changes of anti-NBL and anti-acetylcholine receptor (AChR) antibody titers could be observed during the follow-up period in MG patients positive for both types of antibodies. These findings further emphasize the immunological complexity of MG. Anti-NBL antibodies represent a pathogenic marker of the disease and display a regulation different from that of the anti-AChR antibodies.     

Do GM1 antibodies induce demyelination?

We review clinical, neurophysiological, immunological, and experimental data concerning multifocal motor neuropathy (MMN), a newly recognized disorder that mimics MND. It is separated from MND by the presence of multifocal conduction block (CB) demonstrated electrophysiologically, and in some instances by the association of high liters of GM₁ antibodies. The possible immunopathogenetic effect of GM₁ antibodies is discussed. However, 70% of patients with MMNCB do not have elevated titers of GM₁ antibodies, but may respond nevertheless to immunosuppressive treatment. Thus, so far unrecognized antibodies may react against some other epitopes in the paranodal region than those attacked by GM₁ antibodies to cause CB. © 1994 John Wiley & Sons, Inc.     

Peripheral neuropathy associated with IgM monoclonal gammopathy: Correlations between M-protein antibody activity and clinical/electrophysiological features in 40 cases

Forty cases of polyneuropathy associated with IgM monoclonal gammopathy were retrospectively studied to investigate the relevance of clinical and electrophysiological features to M-protein antibody activity. There were 26 men and 14 women; mean age was 65 ± 11.7 years at the time of the study. Thirty-nine patients had a symmetrical polyneuropathy, of whom 13 had a predominantly sensory and 17 a purely sensory neuropathy (i.e., 30 sensory neuropathies). The remaining patient had a multifocal mononeuropathy. Electrophysiological studies allowed the polyneuropathies to be classified as demyelinating in 33 cases (82.5%) and axonal in 6 cases. Antibody studies disclosed anti-MAG antibodies in 65% and anti-SGPG antibodies in 82.5% of patients. Anti-MAG antibodies were associated with only demyelinating polyneuropathies. Anti-SGPG antibodies were found in 91% of demyelinating polyneuropathies and 50% of axonopathies. In addition, anti-MAG/SGPG antibody activity was significantly correlated with the subgroup of sensory neuropathies (P < 0.01). Last, antisulfatide antibodies were found at significant titers in 18 cases, and their presence was significantly correlated with anti-MAG/SGPG antibody activity, but not with some clinical/electrophysiological features. © 1998 John Wiley & Sons, Inc. Muscle Nerve, 21: 55–62, 1998.     

Non‐anti‐MAG DADS neuropathy as a variant of CIDP: clinical,electrophysiological, laboratory features and response to treatment in 10 cases

Background and purpose: Some patients within the spectrum of chronic inflammatory demyelinating polyradiculoneuropathies (CIDP) have distal acquired demyelinating symmetric (DADS) neuropathy, usually associated with anti‐myelin‐associated‐glycoprotein (MAG) IgM monoclonal gammopathy. The aim of this retrospective study was to investigate patients with DADS neuropathy without anti‐MAG antibodies, and study their response to immunotherapy. Methods: Patients were selected on the basis of (i) ‘Definite CIDP’ according to the EFNS/PNS Guideline criteria, (ii) The presence of disproportionately prolonged motor latencies resulting in a terminal latency index (TLI) ≤0.25 in at least two motor nerves and (iii) The absence of anti‐MAG antibodies on ELISA. Response to immunotherapy was defined as persistent improvement by at least one point on the INCAT disability score. Results: Data from 146 CIDP patients were analysed, and 10 patients were included. Six had clinically pure sensory neuropathy, and four had sensorimotor neuropathy. Ataxia was present in nine patients, generalized areflexia in seven and postural tremor in two. Five of the 10 patients had abnormal sensory potentials only in the upper limbs. An associated condition was found in nine patients: two chronic lymphocytic leukaemias, four IgG monoclonal gammopathies (one associated with non‐Hodgkin’s lymphoma) and two IgM monoclonal gammopathies of unknown significance. Patients were mostly improved with intravenous immunoglobulin (IVIg), corticosteroids, plasma exchanges, or a combination thereof. Conclusion: DADS neuropathy without anti‐MAG antibodies is more likely to be considered a variant of CIDP. In addition, such patients should be systematically investigated for an associated haematological or immunological condition.     

Clinical and genetic associations of autoantibodies to 3‐hydroxy‐3‐methyl‐glutaryl‐coenzyme a reductase in patients with immune‐mediated myositis and necrotizing myopathy

Introduction: Inhibition of 3‐hydroxy‐3‐methyl‐glutaryl‐coenzyme A reductase (HMGCR) with statins may trigger idiopathic inflammatory myositis (IIM) or immune‐mediated necrotizing myopathy (IMNM). Anti‐HMGCR antibodies have been detected in patients with IIM/IMNM. We aimed to determine the associations of anti‐HMGCR in IIM/IMNM. Methods: Anti‐HMGCR antibodies were detected by ELISA in sera from patients with IIM/IMNM. Results: Anti‐HMGCR antibodies were detected in 19 of 207 patients with IIM/IMNM, and there was a trend toward an association with male gender (P = 0.079). Anti‐HMGCR antibodies were associated strongly with statin exposure (OR = 39, P = 0.0001) and HLA‐DRB1*11 (OR = 50, P < 0.0001). The highest risk for development of anti‐HMGCR antibodies was among HLA‐DR11 carriers exposed to statins. Univariate analysis showed a strong association of anti‐HMGCR antibodies with diabetes mellitus (P = 0.008), which was not confirmed by multiple regression. Among anti‐HMGCR⁺ patients there was a trend toward increased malignancy (P = 0.15). Conclusions: Anti‐HMGCR antibodies are seen in all subtypes of IIM and IMNM and are associated strongly with statin use and HLA‐DR11. Muscle Nerve 52 : 196–203, 2015     

IgM monoclonal gammopathy–associated neuropathies with different IgM specificity

Background and purpose: Antibodies directed against myelin‐associated glycoprotein (MAG) are believed to be the most frequent biologic marker of the neuropathies associated with IgM monoclonal gammopathy of undetermined significance (MGUS). The objective of this study was to examine the prevalence of antiganglioside and/or sulfatide‐positive patients and their clinical findings, including therapeutic response, compared to anti‐MAG‐positive or seronegative patients. Methods: We prospectively followed 46 patients with MGUS who were diagnosed in our tertiary referral centers for polyneuropathy since 1997. All patients underwent nerve conduction studies and were tested for anti‐MAG, gangliosides, and sulfatide antibodies. All the anagraphic and clinical data (including symptoms, disability scale, therapy, secondary malignancy development) were recorded in a database and compared between three patients’ groups (anti‐MAG‐positive; antiganglioside/sulfatide‐positive; no reactivity). Results: Anti‐MAG reactivity was present in 17 (37%) patients; other 17 patients (37%) had antiganglioside/sulfatide reactivity and 12 (26%) had no reactivity. Patients with antiganglioside/sulfatide positivity, although heterogeneous by a clinical and neurophysiological point of view, had the most severe neuropathic manifestations and a higher disability score at nadir (P < 0.001). These patients had a better response to both intravenous immunoglobulin therapy and rituximab. Conclusions: Our results suggest that antiganglioside/sulfatide‐positive patients form a relevant portion of patients with MGUS‐associated polyneuropathy seen in tertiary care centers and should be considered in future studies on treatment response.     

Anti‐ganglioside antibodies in Guillain–Barré syndrome and chronic inflammatory demyelinating polyneuropathy in Chinese patients

Introduction: In this study we investigated the relationships between anti‐ganglioside antibodies and Guillain–Barré syndrome (GBS) and chronic inflammatory demyelinating polyneuropathy (CIDP). Methods: Samples from 48 Chinese patients diagnosed with GBS and 18 patients diagnosed with CIDP were retrospectively reviewed. Results: In the GBS patients, 62.5% were classified as having acute inflammatory demyelinating polyneuropathy (AIDP), 27.1% were found to have acute motor axonal neuropathy (AMAN), and 10.4% were unclassified. Serum IgG anti‐ganglioside antibodies were detected in 46.2% of the AMAN patients and in 6.7% of the AIDP patients (P < 0.05); 5.6% of the 18 CIDP patients were IgG antibody positive, and 27.8% were IgM antibody positive. Facial palsy and sensory impairment were significantly associated with IgM antibodies. Conclusions: These results suggest that IgG anti‐GM1 antibodies are associated with AMAN, but not with AIDP, and that IgM antibodies against GM1, GM2, and GM3 are associated with facial nerve palsy. Muscle Nerve 55 : 470–475, 2017     

Search for specific anti-MS IgG antibodies

An antiserum against purified IgG from pooled MS sera was produced in a rabbit. The anti MS-IgG serum was absorbed with different antibodies in order to demonstrate residual antibodies directed against the hypervariable region of the MS-IgG molecules. The antigens used for absorption were: normal sera, normal infant sera (without measles antibodies), IgG myeloma proteins. All the antigens used determined the complete disappearance of the precipitating anti-MS IgG antibodies.

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Sommario è stato prodotto da un coniglio un antisiero contro IgG purificata da sieri di pazienti affetti da sclerosi multipla. Tale siero (anti Ms-IgG) è stato assorbito con diversi anticorpi allo scopo di dimostrare eventuali anticorpi residui diretti specificamente contro Ms-IgG. Per tale assorbimento sono stati usati i seguenti antigeni: siero normale, siero di lattanti (senza anticorpi anti-morbillo), sieri di mieloma IgG. Tutti gli antigeni impiegati hanno determinato la scomparsa completa degli anticorpi precipitanti anti Ms-IgG.

     

Frequency and significance of anti-Ro (SS-A) antibodies in multiple sclerosis patients

OBJECTIVE: To determine the frequency and significance of antinuclear (ANA), anticardiolipin (ACA) and anti-Ro (SS-A) antibodies in multiple sclerosis (MS) patients. METHODS: ANA (indirect immunofluorescence), ACA and anti-Ro (SS-A) antibodies (ELISA) were tested in sera of 42 patients with Poser defined MS and 50 healthy individuals. RESULTS: High levels of anti-Ro (SS-A) antibodies were found in 3 patients (7%) (vs 0 in the control group). Two of them had normal salivary gland biopsy. Clinical MS form was chronic-progressive in 2 cases and relapsing-remitting in the third one. Ten patients (23%) had low levels of ANA (vs 4%), none of them positive for anti-Ro (SS-A) antibodies. Only 1 patient (2%) with RR clinical form had ACA (vs 0). No clinical or neuroradiological differences with conventional MS patients were observed. CONCLUSIONS: ANA, ACA and anti-Ro (SS-A) antibodies in MS patients indicate an underlying autoimmune disease but our series suggests that they are an epiphenomenon of a more diffuse immunological dysfunction.     

Myopathy associated with anti-signal recognition peptide antibodies: clinical heterogeneity contrasts with stereotyped histopathology

We report three patients with anti-signal recognition particle antibodies who had different presenting clinical pictures, mimicking acute polymyositis, limb-girdle muscular dystrophy, and acute rhabdomyolysis. Muscle biopsies typically showed necrotizing myopathy with little or no inflammation and deposits of membrane attack complex (C5b-9) in endomysial capillaries. The clinical course was severe in two patients and mild in one. The combination of corticosteroid with either an immunosuppressive agent or intravenous immunoglobulins was required to improve the condition of these patients.     

Anti-GM1 antibodies in patients with chronic inflammatory demyelinating polyneuropathy (CIDP) treated with intravenous immunoglobulin (IVIg)

Patients with chronic inflammatory demyelinating polyneuropathy (CIDP) and with a chronic polyneuropathy (non-CIDP) were studied for the presence of anti-GM1 antibodies. In pretreatment sera of CIDP patients, we found IgG anti-GM1 antibodies in 23%, IgM in 7%, and IgA in 14%. Predominantly motor involvement was associated with IgG and IgM anti-GM1 antibodies in CIDP patients (P = 0.002). Improvement after intravenous immunoglobulin (IVIg) therapy was not associated with anti-GM1 antibody titer before or after treatment. Anti-GM1 antibody titers before onset of treatment was not related to poor clinical outcome, although large clinical improvements after IVIg therapy were observed less often (P = 0.057) in patients with high titer anti-GM1 antibodies before treatment.     

Autoantibodies against the Hel-N1 RNA-binding protein among patients with lung carcinoma: An association with type I anti–neuronal nuclear antibodies

Hel-N1 is a novel human complementary DNA encoding a neuronal RNA-binding protein which shares considerable sequence homology with the HuD protein, a target of type I anti–neuronal nuclear antibodies in patients with paraneoplastic encephalomyelitis. The aim of the present study was to determine the prevalence of antibodies against the Hel-N1 protein among patients with lung carcinoma, including those with paraneoplastic disorders. Sera from 45 patients with lung cancer (42 with small-cell carcinoma) and from 28 control patients with other neurological diseases were studied by enzyme-linked immunosorbent assay (ELISA) and by immunoblotting with recombinant Hel-N1 protein. Sixteen of the 45 lung cancer patients (14 with small-cell and 2 with undifferentiated carcinoma) had paraneoplastic encephalomyelitis and high-titer type I anti–neuronal nuclear antibodies; sera from each of these 16 patients also showed strong reactivity with Hel-N1 protein. The other 29 lung cancer patients, all of whom had neurological dysfunction and 24 of whom had known or suspected paraneoplastic disorders, lacked the type I antibody by standard testing. The mean anti–Hel-N1 titer (by ELISA) of sera from patients negative for type I anti–neuronal nuclear antibody was significantly less than that of the patients positive for the type I antibody, but exceeded that of the control patients with other neurological diseases (p < 0.001). Fifteen (52%) of the 29 type I antibody–negative patients had positive serum anti–Hel-N1 titers which did not overlap the high anti–Hel-N1 titers of the 16 type I antibody–positive patients. These findings support the theory that type I anti–neuronal nuclear antibodies react with a family of neuronal RNA-binding proteins, and suggest that these proteins share one or more epitopes. High titers of circulating anti–Hel-N1 antibodies correlate with paraneoplastic encephalomyelitis, while lower anti–Hel-N1 titers are present in a sizeable proportion of patients with small-cell lung cancer without a clear association with their clinical condition.