Intrathecal synthesis of oligoclonal IgM against myelin lipids predicts an aggressive disease course in MS

Villar, Luisa María; Sádaba, María C.; Roldán, Ernesto; Masjuán, Jaime; González-Porqué, Pedro; Villarrubia, Noelia; Espiño, Mercedes; García-Trujillo, José Antonio; Bootello, A; Álvarez‐Cermeño, José C.

doi:10.1172/jci22833

Cited by 234 publications

(141 citation statements)

References 43 publications

Supporting

Mentioning

130

Contrasting

Order By: Relevance

“…These authors failed to demonstrate Toxoplasma gondii-specific fLC in AIDS patients with T. gondii encephalitis using IEF/AIB:although o-fLC were found in all patients; antigen-specific fLC were demonstrated by ELISA instead. The way Villar et al described CSF-restricted lipid-specific oligoclonal IgM bands 57 , we can speculate whether CSF-restricted fLC could have the same specificity.…”

Section: Discussionmentioning

confidence: 81%

Oligoclonal free light chains in cerebrospinal fluid as markers of intrathecal inflammation. Comparison with oligoclonal IgG

Zeman¹,

Hradílek²,

Kušnierová³

et al. 2015

Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub

View full text Add to dashboard Cite

Aims.To compare the sensitivity and specificity of CSF-restricted oligoclonal IgG and free light chains as markers of multiple sclerosis and other inflammatory neurological diseases. Methods. 196 paired CSF and serum samples were examined for oligoclonal IgG and oligoclonal free light chains. The sensitivity and specificity of the tests were calculated and optimal cut-offs for the number of CSF-restricted oligoclonal bands were then determined by analysis of receiver operating characteristic curves. Results. Optimal cut-off values were ≥5 IgG bands for multiple sclerosis, ≥4 IgG bands for inflammatory neurological disease, ≥6 free κ, and ≥2 free λ bands for both purposes. Using these cut-off values, sensitivities and specificities for multiple sclerosis were 83.8% and 91.3% for IgG, 83.8% and 81.0% for free κ , and 67.6% and 75.4% for free λ. For inflammatory neurological disease, sensitivities and specificities were 60.8% and 95.7% for IgG, 69.6% and 92.6% for free κ, and 64.8% and 86.2% for free λ. Conclusions. Although exact cut-off values may vary according to method, reporting borderline results as positive, may compromise the specificity of the test and should be avoided.. The detection of intrathecal free light chain synthesis may be of value especially when the oligoclonal IgG test is negative or borderline, even though its specificity is slightly lower.

show abstract

Section: Discussionmentioning

confidence: 81%

Oligoclonal free light chains in cerebrospinal fluid as markers of intrathecal inflammation. Comparison with oligoclonal IgG

Zeman¹,

Hradílek²,

Kušnierová³

et al. 2015

Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub

View full text Add to dashboard Cite

show abstract

“…22 CSF IgM OCBs can also be found in a subset of patients with pediatric-and adult-onset MS. In adults their presence has been associated with more active/ aggressive disease, 23 but such an association has not been established in pediatric MS. 24 Of note, CSF exhibits age-related changes independent of MS disease mechanisms, particularly around puberty. Reiber et al 20 showed that the amount of intrathecal IgG doubles during puberty because of an increase in the albumin quotient, which represents normal physiologic growth.…”

Section: General Aspects Of Cns Inflammatory Demyelinating Diseases Mmentioning

confidence: 99%

Immunopathophysiology of pediatric CNS inflammatory demyelinating diseases

et al. 2016

View full text Add to dashboard Cite

Elucidating pathophysiologic mechanisms underlying the spectrum of pediatric-onset CNS demyelinating diseases, particularly those that may distinguish multiple sclerosis (MS) from other entities, promises to both improve diagnostics and guide more-informed therapeutic decisions. Observations that pediatric-and adult-onset MS share the same genetic and environmental risk factors support the view that these conditions represent essentially the same illness manifesting at different ages. Nonetheless, special consideration must be given when CNS inflammation manifests in early life, at a time when multiple organs (including immune and nervous systems) are actively maturing. CSF analysis in pediatric-onset MS points to chronic CNS inflammation, supported by observations from limited pathologic material available for study. Emerging results implicate abnormalities in both effector and regulatory T cell subsets, and potentially immune senescence, in children with MS. Although CNS-directed antibodies (including antibodies recognizing myelin antigens; Kir4.1) can be documented in pediatric-onset MS, their pathophysiologic significance (as in adults) remains unclear. This is in contrast to the presence of serum and/or CSF antibodies recognizing aquaporin-4, which, when measured using validated cell-based assays, supports the diagnosis of a neuromyelitis optica spectrum disorder, distinct from MS. Presence of anti-myelin oligodendrocyte glycoprotein antibodies documented with similar cell-based assays may also be associated with pathophysiologically distinct disease phenotypes in children. The substantial impact of pediatriconset MS on normal brain development and function underscores the importance of elucidating both the immunobiology and neurobiology of disease. Ongoing efforts are aimed at developing and validating biological measures that define pathophysiologically distinct monophasic and chronic forms of pediatric CNS demyelination. Neurology ® 2016;87 (Suppl 2):S12-S19 GLOSSARY ADEM 5 acute disseminated encephalomyelitis; AQP4 5 aquaporin-4; BBB 5 blood-brain barrier; CBA 5 cell-based assay; EDSS 5 Expanded Disability Status Scale; MBP 5 myelin basic protein; MOG 5 myelin oligodendrocyte glycoprotein; MS 5 multiple sclerosis; NMO 5 neuromyelitis optica; NMOSD 5 NMO spectrum disorder; OCB 5 oligoclonal band; ON 5 optic neuritis; OPC 5 oligodendrocyte precursor cell; TM 5 transverse myelitis.There is presently limited insight into the pathophysiologic mechanisms underlying childhoodonset inflammatory demyelinating diseases. Because these disorders occur in the context of the developing immune and nervous systems, understanding the implications to both disease mechanisms and efficacy and safety profiles of potential therapeutics will help guide optimal management approaches for these children and adolescents. Elucidating the biology of pediatric-onset multiple sclerosis (MS) may provide key insights into earliest targets and processes involved in disease pathogenesis as well as into the broader spectrum of CNS...

show abstract

“…Binding of OCBs was investigated by immunoblotting with a phosphatase alkaline anti-human IgG Ab for 2h30 (Jackson ImmunoResearch Laboratories, Suffolk, U.K.). OCB reactivity was then explored as described previously (18). Patients were considered as negative when they lacked bands in the SPAG16 blot or showed the same pattern in the SPAG16 and THIO (control) membranes.…”

Section: Isoelectric Focusingmentioning

confidence: 99%

Sperm-Associated Antigen 16 Is a Novel Target of the Humoral Autoimmune Response in Multiple Sclerosis

Bock

Somers

Fraussen

et al. 2014

The Journal of Immunology

Self Cite

View full text Add to dashboard Cite

We have previously identified eight novel autoantibody targets in the cerebrospinal fluid of multiple sclerosis (MS) patients, including sperm-associated Ag 16 (SPAG16). In the current study, we further investigated the autoantibody response against SPAG16—a protein with unknown function in the CNS—and its expression in MS pathology. Using isoelectric focusing, we detected SPAG16-specific oligoclonal bands in the cerebrospinal fluid of 5 of 23 MS patients (22%). Analysis of the anti-SPAG16 Ab reactivity in the plasma of a total of 531 donors using ELISA demonstrated significantly elevated anti-SPAG16 Ab levels (p = 0.002) in 32 of 153 MS patients (21%) compared with all other control groups with 95% specificity for the disease. To investigate the pathologic relevance of anti-SPAG16 Abs in vivo, anti-SPAG16 Abs were injected in mice with experimental autoimmune encephalomyelitis, resulting in a significant disease exacerbation. Finally, we demonstrated a consistent upregulation of SPAG16 in MS brain and experimental autoimmune encephalomyelitis spinal cord lesions, more specifically in reactive astrocytes. We conclude that SPAG16 is a novel autoantibody target in a subgroup of MS patients and in combination with other diagnostic criteria, elevated levels of anti-SPAG16 Abs could be used as a biomarker for diagnosis. Furthermore, the pathologic relevance of anti-SPAG16 Abs was shown in vivo.

show abstract

Intrathecal synthesis of oligoclonal IgM against myelin lipids predicts an aggressive disease course in MS

Cited by 234 publications

References 43 publications

Oligoclonal free light chains in cerebrospinal fluid as markers of intrathecal inflammation. Comparison with oligoclonal IgG

Oligoclonal free light chains in cerebrospinal fluid as markers of intrathecal inflammation. Comparison with oligoclonal IgG

Immunopathophysiology of pediatric CNS inflammatory demyelinating diseases

Sperm-Associated Antigen 16 Is a Novel Target of the Humoral Autoimmune Response in Multiple Sclerosis

Contact Info

Product

Resources

About