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Proposed cut-off for reactivity of anti-HMGCR and anti-SRP antibodies in patients statin-exposed and statin-unexposed.

ABSTRACT: The therapeutic approach with statins is widely used in the control of dyslipidemias. However, there is no laboratory evaluation to elect patients to make use of this class of therapeutic drugs.We analyzed the prevalence of anti-signal recognition particle (anti-SRP) and anti-3-hydroxy-3-methylglutaryl-coenzyme A reductase (anti-HMGCR) antibodies in a heterogeneous cohort of 85 patients in order to determine cutoff reference values for these antibodies.Serum samples from 85 patients were screened for the presence of anti-HMGCR and anti-SRP autoantibodies by enzyme-linked immunosorbent assay. The demographic, clinical, and morphological features were also correlated with anti-HMGCR and anti-SRP antibodies. The patients were divided in 2 groups: A, statin-exposed, and B, statin-unexposed.There was no significant association (P?>?.05) among anti-HMGCR and anti-SRP titers in relation to age, sex, statin exposure, and CK level. The concentrations of both antibodies were not correlated with symptoms, CK level, or statin exposure. Eleven (12.9%) patients had anti-HMGCR antibodies. We found a tendency (P?=?.051) toward greater anti-HMGCR positivity in women with no symptoms. Twelve (14.1%) patients had anti-SRP antibodies. There was no sex predominance, and only 1 patient had muscle complaints. Muscular symptoms were present in 31 (36.5%) patients, 4 (12.9%) were positive for anti-HMGCR antibodies, and 1 (3.2%) was positive for anti-SRP antibodies. A total of 54 (63.5%) patients had no muscle symptoms, 7 (13%) were anti-HMGCR positive, and 11 (20.4%) were anti-SRP positive. We found statistical significance for patients with anti-SRP antibodies when asymptomatic and symptomatic patients were compared (P?=?.029). In contrast, there was no statistically significant difference between symptoms and positivity for anti-HMG antibodies.One of the main aims of this study was to define a cutoff point in a heterogeneous population with different diagnoses. We also demonstrated that anti-HMGCR and anti-SRP antibodies are not 100% specific to immune-mediated necrotizing myopathy. We believe that these antibodies must be tested and interpreted within the specific context.

SUBMITTER: Carvalho AAS

PROVIDER: S-EPMC6392535 | biostudies-literature | 2018 Aug

REPOSITORIES: biostudies-literature

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Proposed cut-off for reactivity of anti-HMGCR and anti-SRP antibodies in patients statin-exposed and statin-unexposed.

Carvalho Alzira Alves Siqueira AAS Silva Vinicius Gomes da VGD Vieira Thaiane Fagundes TF Delgado Pamela Oliveira PO Corazini Roseli R Feder David D Fonseca Fernando Luiz Affonso FLA

Medicine 20180801 35

The therapeutic approach with statins is widely used in the control of dyslipidemias. However, there is no laboratory evaluation to elect patients to make use of this class of therapeutic drugs.We analyzed the prevalence of anti-signal recognition particle (anti-SRP) and anti-3-hydroxy-3-methylglutaryl-coenzyme A reductase (anti-HMGCR) antibodies in a heterogeneous cohort of 85 patients in order to determine cutoff reference values for these antibodies.Serum samples from 85 patients were screene ...[more]

PMID: 30170376

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Project description:BackgroundAnti-drug antibodies (ADAs) to bococizumab were detected in > 40% of subjects in the SPIRE lipid-lowering trials. The risk of cross-reactivity between anti-bococizumab antibodies and other approved anti-proprotein convertase subtilisin/kexin type-9 (PCSK9) monoclonal antibodies (mAbs) was investigated using a single-assay approach.MethodsBococizumab immunogenicity was assessed in SPIRE-HR, a 52-week study. The highest ADA titer sample from each ADA-positive subject (n = 155) was tested in vitro for cross-reactivity to alirocumab and evolocumab using a novel ADA assay approach. Additional specificity tiers within the bococizumab ADA assay against each drug were validated using recombinant PCSK9 as a surrogate cross-reactive positive control. If the highest ADA titer sample showed cross-reactivity, additional samples from that subject were analyzed. Cross-reactivity was determined by the ability of alirocumab or evolocumab to inhibit the sample signal greater than or equal to the cross-reactivity cut-points.ResultsADAs were detected in 44.0% (155/352) of bococizumab-treated subjects, and 27.0% also developed neutralizing antibodies (NAbs). Median ADA and NAb titers ranged from 276 to 526 and 8 to 12 over the course of the study, respectively. From 155 ADA-positive subjects tested for cross-reactivity, one (0.6%) subject showed weak cross-reactivity to both alirocumab and evolocumab. This cross-reactivity signal was transient (from Days 337 to 373) and undetectable at the last ADA-positive timepoint (Day 407).ConclusionA novel, single-assay approach was validated to assess the potential cross-reactivity of anti-bococizumab antibodies to alirocumab and evolocumab. In subjects who developed ADAs to bococizumab, the likelihood of clinically relevant cross-reactivity to marketed anti-PCSK9 mAbs is remote, based on the low frequency of cross-reactivity observed, which was weak in signal inhibition and transient in nature.Clinical trial registrationThe SPIRE-HR study is registered on ClinicalTrials.gov under the identifier NCT01968954.

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Proposed cut-off for reactivity of anti-HMGCR and anti-SRP antibodies in patients statin-exposed and statin-unexposed.

Publications

Proposed cut-off for reactivity of anti-HMGCR and anti-SRP antibodies in patients statin-exposed and statin-unexposed.

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