Welcome to the 13th International Congress on Autoimmunity interactive program

Background and Aims

Idiopathic inflammatory myopathies (IIMs) are rare systemic diseases associated with significant morbidity and mortality. The aim of our observational study was to estimate for the first time the survival of IIM patients in Slovenia.

Methods

We included IIM patients diagnosed between Jan/2005 and Dec/2020, and followed at two secondary/tertiary rheumatology centers in the country. To study survival the censor date of April 14, 2021, was set. Kaplan–Meier analysis and standardized mortality ratio (SMR) were plotted using data of age and sex matched Slovenian population as a reference. Cox proportional hazards regression analysis was used to study prognostic factors for death.

Results

During the 16-year observation period, we identified 217 IIM patients. During follow up 65 (30.0%) patients died. One- and five-year survival rate was 88.9% and 75.5%, respectively. In the first year following IIM diagnosis the SMR was nearly 7-fold higher compared to the matched general population (SMR 6.88 (95%CI 4.41–10.24)) and remained higher also during the following 4 years. However, when excluding IIM patients with cancer, the survival outcome was, except in the first year after IIM diagnosis (SMR 5.55 (95%CI 3.10 – 9.15)), comparable to matched general population. In addition to cancer (HR 3.71 (95% CI 2.18–6.04)), cardiac involvement (HR 2.18 (95% CI 1.07 – 4.45)), fever (HR 2.13 (95% CI 1.13 – 4.03)) and age (HR 1.07 (95% CI 1.04 – 1.09)) emerged as prognostic factors associated with death.

Conclusions

The overall survival of IIM patients was worse compared to matched general population. Cancer was the leading cause of death in our cohort.

Background and Aims

Idiopathic inflammatory myositis (IIM) is a group of heterogeneous autoimmune diseases, characterized by myositis-specific (MSA) or myositis-associated autoantibodies (MAA). Muscle biopsy is the diagnostic gold standard test, but correlations with elevated creatine level (CK) or MSA/MAA are unknown. The aim was to evaluate the association between histological findings and clinical and/or serological features in IIM patients.

Methods

We retrospectively analyzed demographic and clinical data of 184 IIM patients, followed-up for >1 year. Eighty-nine muscle biopsies were retrieved from deltoid, biceps or quadriceps muscle, snap-frozen and stored at -80°C and processed for routine histology and histochemistry.

Results

Dermatomyositis (DM) was characterized by minimal inflammation and/or necrosis, but prevalent picture of perifascicular atrophy. Polymyositis showed more endomysial infiltration and necrosis. Anti-synthetase syndrome (ASS) patients presented atrophy and perifascicular necrosis in 83%, associated with perimysial and perivascular infiltration in 67% of cases. Those characteristics were observed both in anti-Jo-1+ as well as non-Jo-1+ ASS patients. Non-Jo-1+ ASS presented endomysial infiltration, invading or enveloping the muscle fibers (not present in anti-Jo-1+)(p:0.036). In DM, anti-Mi2 antibodies are significantly associated with perifascicular regeneration and endomysial infiltration, in comparison to both anti-TIF1gamma and anti-NXP2. No significant histopathological features were found in patients with anti-Ro52, that represented the most frequent MAA in our cohort.

Conclusions

No significant associations emerged between CK levels, different types of IIM and MSA. Some histological features seem to define subtypes of DM. A precise definition of autoantibody profile in IIM could define not only a clinical phenotype but also the muscle damage distribution.

Background and Aims

BACKGROUND AND AIMS: In inflammatory myopathies (IIM) MSA or MAA are present in 60-65% of cases (1). Aim of the work is to evaluate the MSA/MAA positivity rate on sera analyzed by immunoblotting (IB), the associated clinical diagnoses and the consistency with the antibody specificity.

Methods

MATERIALS AND METHODS: 267 sera were analyzed using IB (Myositis Antigens Profile 3 (IgG) EUROLINE, Euroimmun) between March 2017 and March 2021. The diagnosis was identified by analyzing the medical records.

Results

RESULTS: A positivity for at least one MSA/MAA was found in 118/267 sera (44.2%); MAA isolated in 22% of cases and a double/multiple positivity for MSA in 12.7%.

The distribution of antibody positivity is shown in Table 1.

The consistency between antibody specificity with the clinical diagnoses was analyzed: for some antibodies, as anti-Jo-1, anti-MDA5 and anti-Tif-1gamma, IB results were consistent with clinical diagnoses (80% for anti-Jo-1 and 75% for anti-MDA5 and anti-Tif-1gamma); while for others, as anti-Mi-2 (18,6%) and anti-SRP (12,5%), the agreement was lower.

Conclusions

CONCLUSIONS: The use of commercial test in the diagnostic workout of IIM has expanded the diagnostic possibilities for these disease conditions. However, with the use of IB, a higher prevalence of double/multiple MSA positivity was found, compared to the 0.1% described with immunoprecipitation (2). Consistency between MSA results and clinical diagnosis was heterogeneous, with the least agreement for anti-Mi-2 and anti-SRP.

References

Betteridge Z, et al. J Autoimmun.2019;101:48-55

Cavazzana I, et al. J Immunol Methods.2016;433:1-5

Background and Aims

SARS-CoV-2 is a RNA virus that associates with heterogeneous clinical manifestations and complications, including autoimmune features. Autoantibodies are identified in approximately 50% of patients with COVID-19. The present study aimed to evaluate the global incidence of myositis-related auto-antibodies (RNA synthetases: anti-PL7, anti-PL12, anti-EJ, anti-OJ and RNA-sensor: anti-MDA5) in our laboratory during COVID-19 pandemics.

Methods

A retrospective study was performed from 2015 to 2021 in a cohort of 444 patients with suspected autoimmune myositis. The incidence of positive results for the antibodies expressed as absolute value was calculated every year. Serum samples were qualitatively analyzed by immunoblotting using EuroBlotOne (Euroimmun, Lubeck, Germany).

Results

The incidence of positive autoantibodies was: 2015: 9; 2016: 24; 2017: 0; 2018: 2; 2019: 1; 2020: 35; 2021: 37. In 2020, the most common antibody detected was anti-MDA5 (54.28% of positive results), followed by anti-PL7 (25.71%); whereas in 2021, anti-PL7 was the most common (35.13[CdS1] % of positive results), followed by anti-PL12 (27.02%) and anti-MDA5 (24.32%). Most patients had clinical manifestations compatible with interstitial lung disease. All positive anti-synthetases patients in 2021 were fully vaccinated (only 2 with previous documented infection), with median time from vaccine to antibodies positivity of 5 months.

Conclusions

Our preliminary data show an increased incidence of myositis-related antibodies against RNA-synthetases and RNA-sensors since the beginning of the COVID-19 pandemic and SARS-CoV-2 vaccination. Differential profile of myositis-associated autoantibodies specificities were observed between 2020 and 2021. Further studies are needed to support the association between SARS-CoV-2 infection and/or vaccination and the presence of these autoantibodies.

Background and Aims

Pneumopathy could be the first and only manifestation of idiopathic inflammatory myopathies (IIMs). Myositis-specific (MSA) or myositis-associated (MAA) autoantibodies are found in 60%-65% of cases [1]. Aim of this work is to evaluate the presence of: MSA/MAA in patients with interstitial lung disease (ILD), a concomitant connective tissue disease (CTD) and the consistency of these diagnoses with antibody specificity.

Methods

Between March 2017 and March 2021, 267 sera were analyzed for MSA/MAA, 84 (31.4%) of which requested after a pneumological evaluation. MSA/MAA were evaluated by IB (EUROLINE, Autoimmune Inflammatory Myopathies 16 Ag Profile). Medical records were analyzed and diagnosis divided in: CTD, interstitial pneumonia with autoimmune features (IPAF) or only pneumological diagnosis.

Results

A positivity for at least one MSA/MAA was found in 37/84 sera (44%) in patients that had the following pneumological diagnosis: 13 non-usual interstitial pneumonia NSIP (35.1%), 10 usual interstitial pneumonia UIP (27%), 10 organizing pneumonia OP (27%), 1 acute interstitial pneumonia (AIP,2.7%), 1 lymphoid interstitial pneumonia (LIP,2.7%), 1 iatrogenic ILD (2.7%), 1 IPAH (2.7%).

Distribution of antibodies is reported in table 1. The most frequent antibody was anti-Ro52 (13,35.2%) while Mi-2 was the most frequent MSA (10,32.4%).

During the diagnostic work-up 13 CTD (35%) and 5 IPAF (13%) were diagnosed; whereas 19 were confirmed as only pneumological diagnosis (51%).

Conclusions

Pneumopathy could be the first manifestation of CTD: research of MSA/MAA and collaboration between rheumatologist and pneumologist allows a correct diagnosis and therapeutic approach.

References

1. Betteridge Z, et al. J Autoimmun 2019;101:48-55

Background and Aims

Multiple sclerosis (MS) is mainly involved in neuroinflammation and demyelination of CNS, in which remyelination failure results in persistent neurological impairment. Fasudil has been shown to have beneficial effects in several models of neurological diseases. In this study, the therapeutic potential and possible mechanisms of Fasudil for remyelination were explored through modulation of astrocytic polarization in cell and animal models.

Methods

The effects of Fasudil on primary astrocytes induced by inflammatory factors were explored. Then these effects were further confirmed in CPZ-induced mice model. CPZ diet was prepared for C57BL/6 mice, which were divided into CPZ and Fasudil group. Fasudil (40 mg/kg/d) was injected intraperitoneally after fifth week of CPZ diet.

Results

Fasudil not only down-regulated the expression of C3 and CFB, but also up-regulated the expression of S100A10 and Ptx3 in inflammatory factor-induced astrocytes. Fasudil intervention lowered expression of inflammatory cytokines IL-6, TNF-α, and increased expression of anti-inflammatory cytokines IL-10, TGF-β in the supernatants of cultured astrocytes. Fasudil improved anxiety/depression-like behaviors and promoted the remyelination of CPZ mice through affecting the polarization of astrocytes. Meanwhile, Fasudil inhibited the expression of C3/CFB and increased the expression of S100A10/Ptx3 in CPZ-diet brain, promoting the expression of NG2.

Conclusions

Fasudil exerts anti-inflammation and enhances remyelination through inducing astrocytic transformation to A2 phenotype, indicating a potential approach for CPZ-induced demyelination. (Supported by NSF of China 81473577, China Postdoctoral Science Foundation 2020M680912, The Doctoral Research Start-up Fund of Shanxi Bethune Hospital 2021RC033. Ma and Xiao are corresponding authors).

Background and Aims

This is a 63-year-old female patient with a history of acute myeloid leukemia that relapsed after 1 year of treatment. She was treated with a salvage chemotherapy protocol, consolidated with allotransplantation of hematopoietic progenitors (HSCT).

The patient consulted for a 3-week history of marked proximal paraparesis associated with continuous non-radiating low back pain that increased while sitting and with bed-chair transitions.

Musculoskeletal involvement is commonly encountered in Graft-versus-Host Disease (GVHD), including joint/fascia manifestations and neuromuscular complications.

The differential diagnosis of a possible GVHD dermatomyositis versus primary dermatomyositis was considered, and she was hospitalized for etiological study.

Methods

An autoimmunity study was performed based on screening for antinuclear antibodies (ANA) by indirect immunofluorescence, as well as an autoimmune myopathy profile analyzed by immunoblot technique.

Magnetic Resonance Imaging (MRI) of the lower limbs, electromyography and a skin biopsy were also performed.

Results

In the autoimmunity profile we obtained positive ANA with centrosome pattern (AC-24) and positive anti-MDA5 antibodies in the myositis blot. Pre-HSCT tests showed the same ANA pattern but the myositis blot was negative.

Skin biopsy showed interface dermatitis that could not be differentiated between dermatomyositis-like GVHD and primary dermatomyositis.

MRI of the limbs showed a myositis-fasciitis pattern, and the electromyography revealed a primary muscle involvement pattern.

Conclusions

After these findings, the case was classified as a primary dermatomyositis MDA5 post HSCT.

We believe that it`s important to consider that not all cases of inflammatory myopathy after transplantation are GVHD-related, and a diagnosis of primary inflammatory myopathy, although rare, should be considered.