Optimizing Anti-Myelin-Associated Glycoprotein and IgM-Gammopathy Testing for Neuropathy Treatment Evaluation.

Autor:	Klein CJ; From the Department of Neurology (C.J.K., D.D., M.V.P., M.P.S., G.S., M.L.M.), Mayo Clinic, Rochester, MN; Department of Neurology (J.D.T.), Royal Adelaide Hospital, Adelaide, South Australia; Department of Laboratory Medicine and Pathology Mayo Clinic (D.L.M., J.R.M., S.S.), Rochester, MN; Department of Neurology (S.S.), Rambam Medical Center, Haifa, Israel; and Department of Hematology Mayo Clinic Foundation (S.M.A.), Rochester, MN., Triplett JD; From the Department of Neurology (C.J.K., D.D., M.V.P., M.P.S., G.S., M.L.M.), Mayo Clinic, Rochester, MN; Department of Neurology (J.D.T.), Royal Adelaide Hospital, Adelaide, South Australia; Department of Laboratory Medicine and Pathology Mayo Clinic (D.L.M., J.R.M., S.S.), Rochester, MN; Department of Neurology (S.S.), Rambam Medical Center, Haifa, Israel; and Department of Hematology Mayo Clinic Foundation (S.M.A.), Rochester, MN., Murray DL; From the Department of Neurology (C.J.K., D.D., M.V.P., M.P.S., G.S., M.L.M.), Mayo Clinic, Rochester, MN; Department of Neurology (J.D.T.), Royal Adelaide Hospital, Adelaide, South Australia; Department of Laboratory Medicine and Pathology Mayo Clinic (D.L.M., J.R.M., S.S.), Rochester, MN; Department of Neurology (S.S.), Rambam Medical Center, Haifa, Israel; and Department of Hematology Mayo Clinic Foundation (S.M.A.), Rochester, MN., Gorsh AP; From the Department of Neurology (C.J.K., D.D., M.V.P., M.P.S., G.S., M.L.M.), Mayo Clinic, Rochester, MN; Department of Neurology (J.D.T.), Royal Adelaide Hospital, Adelaide, South Australia; Department of Laboratory Medicine and Pathology Mayo Clinic (D.L.M., J.R.M., S.S.), Rochester, MN; Department of Neurology (S.S.), Rambam Medical Center, Haifa, Israel; and Department of Hematology Mayo Clinic Foundation (S.M.A.), Rochester, MN., Shelly S; From the Department of Neurology (C.J.K., D.D., M.V.P., M.P.S., G.S., M.L.M.), Mayo Clinic, Rochester, MN; Department of Neurology (J.D.T.), Royal Adelaide Hospital, Adelaide, South Australia; Department of Laboratory Medicine and Pathology Mayo Clinic (D.L.M., J.R.M., S.S.), Rochester, MN; Department of Neurology (S.S.), Rambam Medical Center, Haifa, Israel; and Department of Hematology Mayo Clinic Foundation (S.M.A.), Rochester, MN., Dubey D; From the Department of Neurology (C.J.K., D.D., M.V.P., M.P.S., G.S., M.L.M.), Mayo Clinic, Rochester, MN; Department of Neurology (J.D.T.), Royal Adelaide Hospital, Adelaide, South Australia; Department of Laboratory Medicine and Pathology Mayo Clinic (D.L.M., J.R.M., S.S.), Rochester, MN; Department of Neurology (S.S.), Rambam Medical Center, Haifa, Israel; and Department of Hematology Mayo Clinic Foundation (S.M.A.), Rochester, MN., Pinto MV; From the Department of Neurology (C.J.K., D.D., M.V.P., M.P.S., G.S., M.L.M.), Mayo Clinic, Rochester, MN; Department of Neurology (J.D.T.), Royal Adelaide Hospital, Adelaide, South Australia; Department of Laboratory Medicine and Pathology Mayo Clinic (D.L.M., J.R.M., S.S.), Rochester, MN; Department of Neurology (S.S.), Rambam Medical Center, Haifa, Israel; and Department of Hematology Mayo Clinic Foundation (S.M.A.), Rochester, MN., Ansell SM; From the Department of Neurology (C.J.K., D.D., M.V.P., M.P.S., G.S., M.L.M.), Mayo Clinic, Rochester, MN; Department of Neurology (J.D.T.), Royal Adelaide Hospital, Adelaide, South Australia; Department of Laboratory Medicine and Pathology Mayo Clinic (D.L.M., J.R.M., S.S.), Rochester, MN; Department of Neurology (S.S.), Rambam Medical Center, Haifa, Israel; and Department of Hematology Mayo Clinic Foundation (S.M.A.), Rochester, MN., Skolka MP; From the Department of Neurology (C.J.K., D.D., M.V.P., M.P.S., G.S., M.L.M.), Mayo Clinic, Rochester, MN; Department of Neurology (J.D.T.), Royal Adelaide Hospital, Adelaide, South Australia; Department of Laboratory Medicine and Pathology Mayo Clinic (D.L.M., J.R.M., S.S.), Rochester, MN; Department of Neurology (S.S.), Rambam Medical Center, Haifa, Israel; and Department of Hematology Mayo Clinic Foundation (S.M.A.), Rochester, MN., Swart G; From the Department of Neurology (C.J.K., D.D., M.V.P., M.P.S., G.S., M.L.M.), Mayo Clinic, Rochester, MN; Department of Neurology (J.D.T.), Royal Adelaide Hospital, Adelaide, South Australia; Department of Laboratory Medicine and Pathology Mayo Clinic (D.L.M., J.R.M., S.S.), Rochester, MN; Department of Neurology (S.S.), Rambam Medical Center, Haifa, Israel; and Department of Hematology Mayo Clinic Foundation (S.M.A.), Rochester, MN., Mauermann ML; From the Department of Neurology (C.J.K., D.D., M.V.P., M.P.S., G.S., M.L.M.), Mayo Clinic, Rochester, MN; Department of Neurology (J.D.T.), Royal Adelaide Hospital, Adelaide, South Australia; Department of Laboratory Medicine and Pathology Mayo Clinic (D.L.M., J.R.M., S.S.), Rochester, MN; Department of Neurology (S.S.), Rambam Medical Center, Haifa, Israel; and Department of Hematology Mayo Clinic Foundation (S.M.A.), Rochester, MN., Mills JR; From the Department of Neurology (C.J.K., D.D., M.V.P., M.P.S., G.S., M.L.M.), Mayo Clinic, Rochester, MN; Department of Neurology (J.D.T.), Royal Adelaide Hospital, Adelaide, South Australia; Department of Laboratory Medicine and Pathology Mayo Clinic (D.L.M., J.R.M., S.S.), Rochester, MN; Department of Neurology (S.S.), Rambam Medical Center, Haifa, Israel; and Department of Hematology Mayo Clinic Foundation (S.M.A.), Rochester, MN.
Jazyk:	angličtina
Zdroj:	Neurology [Neurology] 2024 Dec 10; Vol. 103 (11), pp. e210000. Date of Electronic Publication: 2024 Nov 05.
DOI:	10.1212/WNL.0000000000210000
Abstrakt:	Background and Objectives: Patients with typical anti-myelin-associated glycoprotein (anti-MAG) neuropathy have IgM-gammopathy, mimic distal chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), and are treatment resistant. Anti-MAG patients go unrecognized when IgM-gammopathy is undetected or with atypical phenotypes. We investigated an optimal anti-MAG titration cutoff for excluding CIDP and the impact of IgM-gammopathy detection on neuropathy treatment evaluation without anti-MAG antibodies. Methods: European Academy of Neurology/Peripheral Nerve Society 2021 guidelines were used to assess patients with neuropathy using anti-MAG Bühlmann titration units (BTU) and IgM-gammopathy with Mass-Fix (mass spectrophotometry) and serum protein immunofixation electrophoresis (SPIEP). The immunotherapy outcome was reviewed by inflammatory neuropathy cause and treatment (INCAT) and summated compound muscle action potential (CMAP) nerve conduction changes. Results: Seven hundred and fifty-two patients (average age: 63.8 years, female: 31%) were identified over 30 months: (1) typical anti-MAG neuropathy (n = 104); (2) atypical anti-MAG neuropathy (n = 13); (3) distal or sensory-predominant CIDP (n = 25), including 7 without IgM-gammopathy; (4) typical CIDP (n = 47), including 36 without IgM-gammopathy; (5) axonal IgM-gammopathy-associated neuropathy (n = 104); and (6) IgM-gammopathy-negative, anti-MAG-negative axonal neuropathies (n = 426); and (7) without neuropathy (n = 33) anti-MAG negative. IgM-gammopathy was evaluated by Mass-Fix (n = 493), SPIEP (n = 355), or both (n = 96). Mass-Fix detected 4 additional IgM-gammopathies (3%, 4/117) among patients with anti-MAG antibodies and 7 additional patients (2%, 7/376) without anti-MAG not detected by SPIEP testing. Immunotherapy follow-up was available in 123 (mean: 23 months, range: 3-120 months) including 47 with CIDP (28 without IgM-gammopathy) and 76 non-CIDP (5 without IgM-gammopathy, 45 anti-MAG positive). Treatments included IVIG (n = 89), rituximab (n = 80), and ibrutinib or zanubrutinib (n = 24). An optimal anti-MAG-positive cutoff was identified at ≥1,500 BTU (78% sensitivity, 96% specificity) and at ≥10,000 BTU (74% sensitivity, 100% specificity) for typical anti-MAG neuropathy. Improvements in INCAT scores ( p < 0.0001) and summated CMAP ( p = 0.0028) were associated with negative anti-MAG (<1,500 BTU, n = 78) and absence of IgM-gammopathy (n = 34). Among 47 patients with electrodiagnostically confirmed CIDP, all anti-MAG negative, the presence of IgM-gammopathy (n = 19) also correlated with a worse treatment response (INCAT scores p = 0.035, summated CMAP p = 0.049). Discussion: A cutoff of 10,000 BTU seems optimal for typical anti-MAG neuropathy while ≥1,500 BTU reduces the likelihood of immune-treatable CIDP. Mass-Fix improves IgM-gammopathy detection in anti-MAG and other IgM-gammopathy neuropathies. Patients with IgM-gammopathy lacking MAG antibodies show reduced treatment response.
Databáze:	MEDLINE
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