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  • 1
    In: Rheumatology, Oxford University Press (OUP), Vol. 61, No. 5 ( 2022-05-05), p. 2124-2131
    Abstract: A substantial proportion of RA patients flare upon withdrawal of DMARDs, and thus the definition of prognostic markers is crucial. ACPA positivity has been identified as a risk factor for flare. However, only the role of IgG ACPA is established in this context, while the role of IgA ACPA is poorly defined. We thus aimed to investigate the role of IgA ACPA in flaring of RA. Methods Serum levels of IgA1 and IgA2 ACPA at baseline and after 12 months were measured in 108 patients from the randomized controlled RETRO study. RA patients in stable remission for at least 6 months at study recruitment were assigned to either one of the DMARD tapering arms or to continuation of DMARDs. Results In patients remaining in remission but not in the ones who flared, IgA2 ACPA levels and proportion of IgA2 in ACPA (IgA2% ACPA) significantly declined (median of 17.5%; P  & lt; 0.0001). This seemed to be independent of the treatment choice, as there was no difference in IgA2 ACPA dynamics between the study arms. IgA2% ACPA was associated with disease activity (DAS28) at flare (r = 0.36; P = 0.046). IgA and IgG ACPA showed a tendency towards independent contribution to the risk of flare with the highest risk if a patient had both antibody classes. Conclusion In this study, IgA ACPA was identified as a risk factor for flare in combination with IgG ACPA. IgA2 ACPA levels were associated with flare severity and declined in patients in stable remission.
    Type of Medium: Online Resource
    ISSN: 1462-0324 , 1462-0332
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2022
    detail.hit.zdb_id: 1474143-X
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  • 2
    In: Brain, Oxford University Press (OUP), Vol. 146, No. 4 ( 2023-04-19), p. 1436-1452
    Abstract: Temporal lobe epilepsy (TLE) is one of the syndromes linked to antibodies against glutamic acid decarboxylase (GAD). It has been questioned whether ‘limbic encephalitis with GAD antibodies’ is a meaningful diagnostic entity. The immunopathogenesis of GAD-TLE has remained enigmatic. Improvement of immunological treatability is an urgent clinical concern. We retrospectively assessed the clinical, MRI and CSF course as well as brain tissue of 15 adult patients with GAD-TLE who underwent temporal lobe surgery. Brain tissue was studied by means of immunohistochemistry, multiplex fluorescent microscopy and transcriptomic analysis for inflammatory mediators and neuronal degeneration. In 10 patients, there was a period of mediotemporal swelling and T2 signal increase; in nine cases this occurred within the first 6 years after symptom onset. This resulted in unilateral or bilateral hippocampal sclerosis; three cases developed hippocampal sclerosis within the first 2 years. All CSF studies done within the first year (n = 6) revealed intrathecal synthesis of immunoglobulin G. Temporal lobe surgeries were done after a median disease duration of 9 years (range 3 weeks to 60 years). Only two patients became seizure-free. Brain parenchyma collected during surgery in the first 6 years revealed high numbers of plasma cells but no signs of antibody-mediated tissue damage. Even more dense was the infiltration by CD8+ cytotoxic T lymphocytes (CTLs) that were seen to locally proliferate. Further, a portion of these cells revealed an antigen-specific resident memory T cell phenotype. Finally, CTLs with cytotoxic granzyme B+ granules were also seen in microglial nodules and attached to neurons, suggesting a CTL-mediated destruction of these cells. With longer disease duration, the density of all lymphocytes decreased. Whole transcriptome analysis in early/active cases (but not in late/inactive stages) revealed ‘T cell immunity’ and ‘Regulation of immune processes’ as the largest overrepresented clusters. To a lesser extent, pathways associated with B cells and neuronal degeneration also showed increased representation. Surgically treated patients with GAD-TLE go through an early active inflammatory, ‘encephalitic’ stage (≤6 years) with CTL-mediated, antigen-driven neuronal loss and antibody-producing plasma cells but without signs of complement-mediated cell death. Subsequently, patients enter an apparently immunologically inactive or low-active stage with ongoing seizures, probably caused by the structural damage to the temporal lobe. ‘Limbic encephalitis’ with GAD antibodies should be subsumed under GAD-TLE. The early tissue damage explains why immunotherapy does not usually lead to freedom from seizures.
    Type of Medium: Online Resource
    ISSN: 0006-8950 , 1460-2156
    RVK:
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2023
    detail.hit.zdb_id: 1474117-9
    SSG: 12
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  • 3
    In: Rheumatology, Oxford University Press (OUP), Vol. 61, No. SI ( 2022-04-18), p. SI73-SI80
    Abstract: To compare structural findings between US, micro-CT (µCT) and histology in people with OA of the hands. Methods We analysed DIP and PIP joints of 31 fingers from 15 dissecting-room cadavers with OA of the hands. The occurrence of bone erosions and osteophytes were recorded by US, µCT and histology at 16 regions for each joint and compared for each method. Results In total, US (n = 558, 56.2% of 992 examined regions) and µCT (n = 493, 49.7%) detected a higher frequency of osteophytes at PIP and DIP joints than histology (n = 161, 23.4% of 689 histological examined regions; P = 0.01). We found a comparable number of erosions with each method [US, n = 52 (5.2%); µCT, n = 43 (4.3%); histology, n = 35 (5.2%)]. Both imaging techniques correlated moderately with each other regarding the detection of osteophytes (r = 0.54, P = 0.002) and erosions (r = 0.43, P = 0.017). Neither US nor µCT correlated with histology regarding erosions or osteophytes. With histology as the reference, US had a sensitivity of 80% and a specificity of 32% to detect osteophytes, whereas µCT had a sensitivity of 73% and a specificity of 27%. For erosions, sensitivities (US 10% and µCT 6%, respectively) were much lower. Microscopically, erosions contained fibrous myxoid tissue extending from subcortical cavities through the breach of cortical bone. Conclusions The ability of US to identify osteophytes was comparable to that of µCT, yielding a good sensitivity when histology was used as the gold standard. The sensitivity of US and µCT to detecting erosions was low compared with histology.
    Type of Medium: Online Resource
    ISSN: 1462-0324 , 1462-0332
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2022
    detail.hit.zdb_id: 1474143-X
    Location Call Number Limitation Availability
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