Anti-transcription intermediary factor 1-gamma IgG2 isotype is associated with cancer in adult dermatomyositis: an ENMC multinational study.

OBJECTIVE: To assess the role of the anti-TIF1γ auto-antibody (aAb) IgG2 isotype as a biomarker of cancer in anti-TIF1γ aAb-positive adult DM. METHODS: International multicentre retrospective study with the following inclusion criteria: (i) diagnosis of DM according to ENMC criteria; (ii) presence of anti-TIF1γ IgG aAb determined using an in-house addressable laser bead immunoassay (ALBIA) from cryopreserved serums sampled at time of DM diagnosis and (iii) available baseline characteristics and follow-up data until the occurrence of cancer and/or a minimum follow-up of 1 year for patients without known cancer at diagnosis. Detection and quantification of anti-TIF1γ IgG2 aAb was done using the in-house ALBIA. In addition, a recent ELISA commercial kit was used for anti-TIF1γ IgG aAb quantification. RESULTS: A total of 132 patients (mean age 55±15 years) of whom 72 (54.5%) had an associated cancer were analysed. The association between the presence of cancer and the presence of anti-TIF1γ IgG2 aAb was statistically significant (P = 0.026), with an OR of 2.26 (95% CI: 1.10, 4.76). Patients with cancer displayed significantly higher anti-TIF1γ IgG2 aAb ALBIA values with a median value of 1.15 AU/ml (IQR: 0.14-9.76) compared with 0.50 AU/ml (IQR: 0.14-1.46) for patients without cancer (P = 0.042). In addition, patients with cancer displayed significantly higher anti-TIF1γ IgG aAb ELISA values with a median value of 127.5 AU/ml (IQR: 81.5-139.6) compared with 93.0 AU/ml (IQR: 54.0-132.9) for patients without cancer (P = 0.004). CONCLUSION: These results suggest considering anti-TIF1γ IgG2 ALBIA and IgG ELISA values as biomarkers of cancer in anti-TIF1 γ aAb-positive adult DM.

Tarsal Tunnel Syndrome: Outcome According to Etiology.

Surgical results in tarsal tunnel syndrome are variable, and etiology seems to be a factor. Three possible etiologies can be distinguished. The aim of the present study was to compare surgical results according to etiology. Three continuous retrospective series (45 patients overall) of tarsal tunnel syndrome were compared. Group 1 presented a permanent intra- or extra-tunnel space-occupying compressive structure. Group 2 presented intermittent intra-tunnel venous dilatations. Group 3 comprised idiopathic tarsal tunnel syndrome. The mean follow-up was 3.6 +/- 1.8 years. The main endpoint was subjective postoperative improvement on Likert scale. Group 1 reported greater improvement than groups 2 and 3. Preoperative neuropathy on ultrasound was associated with poorer improvement, which was not the case for neuropathy on electromyography. Surgical treatment of tarsal tunnel syndrome provides better results in etiologies involving structural compression.

A comparative study between isolated gastrocnemius tightness patients and controls by quantitative Gait analysis and baropodometry.

BACKGROUND: Isolated gastrocnemius tightness (IGT) has been suggested as an etiologic factor in mechanical disorders of the foot and ankle without a clear pathophysiological mechanism in the literature. We hypothesized that restricted ankle dorsiflexion inducing increased forefoot pressure in IGT patients could be this pathophysiological mechanism. METHODS: Case/control experimental observational investigation. Forty lower limbs in 20 asymptomatic IGT patients were included and compared to controls. Quantitative gait analyses coupled with dynamic baropodometry were used for comparison between groups. The primary outcome was maximum ankle dorsiflexion during stance phase. Secondary outcomes were knee flexion and forefoot pressure. RESULTS: Maximum ankle dorsiflexion and maximum forefoot pressure were similar between groups. Increased knee flexion was found in the asymptomatic IGT group. CONCLUSIONS: IGT induced compensatory knee flexion during stance phase, which probably prevents increased pressure on the forefoot by allowing ankle dorsiflexion. LEVEL OF EVIDENCE: Level IV, Case/control experimental observational investigation.

Impact of anti-CASPR2 autoantibodies from patients with autoimmune encephalitis on CASPR2/TAG-1 interaction and Kv1 expression.

Autoantibodies against CASPR2 (contactin-associated protein-like 2) have been linked to autoimmune limbic encephalitis that manifests with memory disorders and temporal lobe seizures. According to the growing number of data supporting a role for CASPR2 in neuronal excitability, CASPR2 forms a molecular complex with transient axonal glycoprotein-1 (TAG-1) and shaker-type voltage-gated potassium channels (Kv1.1 and Kv1.2) in compartments critical for neuronal activity and is required for Kv1 proper positioning. Whereas the perturbation of these functions could explain the symptoms observed in patients, the pathogenic role of anti-CASPR2 antibodies has been poorly studied. In the present study, we find that patient autoantibodies alter Caspr2 distribution at the cell membrane promoting cluster formation. We confirm in a HEK cellular model that the anti-CASPR2 antibodies impede CASPR2/TAG-1 interaction and we identify the domains of CASPR2 and TAG-1 taking part in this interaction. Moreover, introduction of CASPR2 into HEK cells induces a marked increase of the level of Kv1.2 surface expression and in cultures of hippocampal neurons Caspr2-positive inhibitory neurons appear to specifically express high levels of Kv1.2. Importantly, in both cellular models, anti-CASPR2 patient autoAb increase Kv1.2 expression. These results provide new insights into the pathogenic role of autoAb in the disease.

Diagnostic yield of commercial immunodots to diagnose paraneoplastic neurologic syndromes.

OBJECTIVE: To investigate the diagnostic yield of commercial immunodots to detect onconeural antibodies associated with paraneoplastic neurologic syndromes (PNSs), we analyzed the proportion of confirmed positive results using alternative techniques. METHODS: Sera (n = 5,300) of patients with suspected PNS were tested by PNS+2 blot (Ravo Diagnostika; January 2016-May 2017) or EUROLINE PNS 12 Ag (Euroimmun; July 2017-November 2018). Positive samples were further explored by in-house indirect immunofluorescence and a third in-house technique (Western blot or cell-based assay) using recombinant protein. Those found negative by these 2 techniques were considered as nonconfirmed. We analyzed the relationship between band intensity and final confirmation. Clinical data were collected for all confirmed results and nonconfirmed EUROLINE immunodots. RESULTS: PNS+2 blot was positive in 128/1,658 (7.7%) sera and confirmed in 47/128 (36.7%). EUROLINE was positive in 186/3,626 (5.1%) and confirmed in 56/186 (30.1%). Confirmation was highly variable among the antibodies tested, from 7.2% (PNS+2 blot) and 5.8% (EUROLINE) for anti-Yo to 88.2% (PNS+2 blot) and 65.0% (EUROLINE) for anti-Hu. None of the 27 weak positive sera by EUROLINE was confirmed. Band intensity in confirmed cases was variable among the antibodies from strong positive for all anti-Yo (n = 3) and anti-Hu (n = 11) to positive (n = 19) or strong positive (n = 9) for anti-SOX1. Among patients with a nonconfirmed EUROLINE result and available clinical information, all had an alternative diagnosis, and only 6.7% had cancer. CONCLUSIONS: Immunodots may be useful for PNS screening, but a threshold should be established for each antibody, and clinical information and confirmation by other techniques are essential. CLASSIFICATION OF EVIDENCE: The study provides Class IV evidence that immunodot assays for onconeural antibodies accurately identify patients with paraneoplastic neurologic syndromes.

Dipotassium ethylenediaminetetraacetic acid is better than tripotassium salt for electrochemiluminescence insulin measurement.

Previous studies reported that stability of insulin was better on ethylenediaminetetraacetic acid (EDTA) plasma sample than serum sample. However, those studies used tripotassium EDTA (K3-EDTA) tubes, rather than dipotassium EDTA (K2-EDTA) tubes which are more commonly used in laboratories. We investigated the impact of preservative type of EDTA (K2 or K3) on the stability of C-peptide and insulin at 4°C and at room temperature room. Our study has identified that K2-EDTA achieves longer stability of insulin but does not improve the stability of C-peptide. Insulin and C-peptide are stable 24h on the same K2-EDTA sample at room temperature.