idiopathic myositis

1. The Importance of Autoantibody Detection
in Autoimmune Inflammatory Myopathies (AIMs)
Immunology Division, Clinical Pathology Department of Dr
Hasan Sadikin Hospital Bandung
2022
Fajar Wasilah

2. • Review : Immune System and Autoimmune Disease
• What are Autoimmune Inflammatory Myopathies (AIMs)
• The Importance of Autoantibody Detection in Autoimmune
Inflammatory Myopathies (AIMs)
Learning Objective

3. Immune System and Autoimmune
Disease

4. Review : Immune System
“ All defensive mechanisms of
the body against invaders, to
regulate and distinguish what
belongs in the body (self) or
what does not (non self/
foreign) in order the body to
function properly, and to
effectively respond as well
as prevent the risk of
illness (Disorders of the
immune system)”.
Homeostas
is
Defens
e
Surveillance
Autoimmun
e
Diseases
Cancer
Infect
ion

5. Review : Immune System

6. Review : Immune System
COLLATERAL
DAMAGE
IMMUNE
REGULATION
Destroy
invadin
g
pathoge
ns
IMMUNE REGULATION
1. Prevent inappropriate
activation, some of
them:
 Immune Tolerance
(Central and
Peripheral Tolerance)
2. Turn off activated
immune system, some of
them:
 T regulatory cells

7. › Normally our body is non responsive to self antigen
› It is called Immunological Tolerance, Normal state of our
body
› Because of breakage of normal immune tolerance , immune
reaction against self antigen occurs that is known as
“Autoimmunity”
› So…Autoimmunity is defined as presence of immune response
against self-tissue
› This term refers to the presence of autoantibodies or auto
reactive T lymphocytes.
› This may be a harmless phenomenon
Autoimmunity & Autoimmune Diseases

8. Development of Autoimmune Diseases
Fairweather D, Autoimmune Disease: Mechanisms., USA ENCYCLOPEDIA OF LIFE SCIENCES & 2007,

9. https://www.scientificame
rican.com/article/the-
terrible-toll-of-76-
The Terrible
Toll of 76
Autoimmune
Diseases
Autoimmune
Diseases

10. What are Autoimmune Inflammatory Myopathies
(AIMs) ?

11. Autoimmune Inflammatory Myopathies (AIMs) : At a
Glance
 Synonym – Idiopathic Inflammatory Myopathies (IIM) or
Myositis, more common type of myopathy
 is a group of rare connective tissue diseases (CTDs) and
heterogeneous group of disorders characterized clinically
by chronic muscle weakness, low muscle endurance and by
inflammatory cell infiltrates in muscle tissue and extra-
muscular signs (joints, skin, lungs and heart).
 The clinical spectrum : wide range of clinical features
 Suggesting that these are systemic autoimmune disease,
referred to Systemic autoimmune rheumatic diseases (SARDs),
as a Connective Tissue diseases Sub group, with the result
that all the clinical manifestations as inflammatory
conditions, associated with autoimmune dysregulation lead
to disability, organ failure and premature mortality.
Nagy H et al. Myopathy. NCBI Bookshelf. StatPearls Publishing; 2022 Jan-
Lega et al. Idiopathic inflammatory myopathies and the lung. Eur Respir Rev 2015; 24: 216–238
Lundberg IE et al. Diagnosis and classification of Idiopathic Inflammatory Myopathies. J Intern Med. 2016 July ; 280(1): 39–51.
Haag et al. How do patients with systemic autoimmune rheumatic disease perceive the use of their medications: a systematic review and
thematic synthesis of qualitative research BMC Rheumatol. 2018; 2: 9.

12. Autoimmune Inflammatory Myopathies (AIMs) :
Clinical Presentation
 Cutaneous features are characteristic
of DERMATOMYOSITIS with
Symmetric rash on the:
› Extensor surfaces of the
hand joints; elbows,
and knees (Gottron
sign); scaly papules; may
form (Gottron papules)
› Upper eyelids (heliotrope rash)
› Upper back, posterior neck, and
shoulders; (shawl sign)
Schmidt J. Current Classification and Management of Inflammatory Myopathies Journal of N

13. Autoimmune Inflammatory Myopathies (AIMs) :
Clinical Presentation
 Limb weakness
› Symmetrical proximal muscle weakness and atrophy
› Commonly affects pelvic and shoulder girdle muscles,
› Can also affect neck muscles (flexors more than
extensors), May be accompanied by myalgia
 Axial muscle weakness
› Oropharyngeal muscle weakness leading to dysphagia
› Respiratory muscle weakness leading to restrictive lung
disease
Polymyositis is by far the rarest form of myositis with an
estimated portion of 5% of all cases
A rash or other signs of inflammation of the skin do not occur
in PM
Schmidt J. Current Classification and Management of Inflammatory Myopathies Journal of N

14. Autoimmune Inflammatory Myopathies (AIMs)
Smoyer-Tomic et al. Incidence and prevalence of idiopathic
inflammatory myopathies among commercially insured,
Medicare supplemental insured, and Medicaid enrolled
populations: an administrative claims analysisBMC

15. As a Rare disease
treatment response is often disappointing
 Persisting muscle weakness
 Functional Impairment
 Low Health related quality of
life
classification criteria are in-correctly
a lack of a diagnosis
Investigating autoimmune
disorders
With myositis recognition of
autoantibodies
as a Biomarker
• History
• Physical examination
• Laboratory examinations
Improve diagnostic precision
 Avoid delay in diagnosis and
treatment
 Reducing a negative impact on
prognosis.
Autoimmune Inflammatory Myopathies (AIMs)

16.  Diagnostic criteria
are meant for clinical
use to aid the
clinician in the
diagnostic workup.
Tanboon al. Where are we moving in the classification of idiopathic inflammatory myopathies?. Review
Update on classification of IIMs?. 2020 Vol 33(5).
Autoimmune Inflammatory Myopathies (AIMs)

17. Autoimmune Inflammatory Myopathies (AIMs)
The EULAR/ACR classification criteria
for adult and juvenile idiopathic
inflammatory myopathies 2017
Lundberg IE et al. Diagnosis and classification of Idiopathic Inflammatory
Oldroyd et al. Recent developments in classification
criteria and diagnosis guidelines for idiopathic
inflammatory myopathieset Review 2018.. www.co-
rheumatology.com Vol 30(6).
Boban & Peter Classification

18. Autoimmune Inflammatory Myopathies (AIMs)
 Diagnostic criteria should be based on clinical and
laboratory manifestations that are present in the patients
early in the disease.
 The new criteria capture the most frequent IIM subgroups and
can be used for both adults and children for research
studies and clinical trials.
 Need to further define the subgroup within AIMs
Simon J-P et al. Autoimmune Myopathies: where Do we Stand? Mini Review. Frontiers in Immunology. 2016. 7:234.
Lundberg IE et al. 2017 European League Against Rheumatism/American College of Rheumatology Classification Criteria for Adult and
Juvenile Idiopathic Inflammatory Myopathies and Their Major Subgroups. ARTHRITIS & RHEUMATOLOGY Vol. 69, No. 12, December 2017, pp
2271–2282

19. The Importance of Autoantibody Detection in Autoimmune
Inflammatory Myopathies (AIMs)

20. Autoimmune Inflammatory Myopathies (AIMs)
Schmidt∗. Current Classification and Management of Inflammatory Myopathies. Journal of Neuromuscular
Diseases 5 (2018) 109–129
OVERVIEW OF THE MAIN ITEMS REQUIRED FOR APPROPRIATE CARE FOR
MYOSITIS

21.  The clinical spectrum of idiopathic inflammatory myopathies
› Due to this heterogeneity, patients with AIMs can present
with varying degrees of muscle disease, cutaneous
manifestations and internal organ involvement
› A wide range of signs and symptoms and clinical features
› Both disease and treatment lead to a poorer health status of
myositis patients in comparison to the general population
Autoimmune Inflammatory Myopathies (AIMs) :
Clinical Aspect
Yoo IS et al.The Role of Autoantibodies in Idiopathic Inflammatory Myopathies. Journal of Rheumatic Diseases.
2019, Vol. 26, No. 3

22. Burbelo PD et al. Autoantibodies Targeting Intracellular
and Extracellular Proteins in Autoimmunity.
Autoantibodies in Autoimmunity.Front. Immunol.2021
Autoantibodies against intracellular proteins are important
disease biomarkers in a number of rheumatological diseases
including Sjögren’s syndrome, systemic lupus erythematosus,
systemic sclerosis, and myositis
Myositis represents a diverse
spectrum of disease subtypes
involving autoimmune-mediated muscle
inflammation and subsequent muscle
tissue destruction.
All known myositis autoantigens that
are targets of autoantibodies are
intracellular proteins.
Autoimmune Inflammatory Myopathies (AIMs) :
Autoantibodies detection

23.  Spectrum of autoantibodies in relation to the clinical spectrum
and disease criteria
Autoantibodies of AIMs, are traditionally divided into :
1. Myositis Specific Autoantibodies (MSA)
MSA are found exclusively in patients with a clinical
diagnosis of AIMs and are generally mutually exclusive. They
are present in up to 50% of AIMs patients.
MSA more specifically help define subgroup of patients are
such as clinical/pathological , phenotype, organ
involvement, prognosis, response to treatment.
2. Myositis-associated autoantibodies (MAA).
Autoimmune Inflammatory Myopathies (AIMs) :
Autoantibodies detection
Damoiseaux J et al. Autoantibodies in idiopathic inflammatory myopathies: Clinical associations and
laboratory evaluation by mono- and multispecific immunoassays. Autoimmunity Reviews 18 (2019) 293–305

24. Z. Betteridge N. McHugh “Myositis-specific autoantibodies: an important tool to support diagnosis of

25. Autoimmune Inflammatory Myopathies (AIMs) :
Antibody Status
 Spectrum of autoantibodies in relation to the clinical spectrum
and disease criteria
Z. Betteridge N. McHugh “Myositis-specific autoantibodies: an important tool to support diagnosis of

26. Autoimmune Inflammatory Myopathies (AIMs) :
Antibody Status

27.  Methods of autoantibody detection
Myositis-specific autoantibodies (MSAs) are routinely detected
by a variety of methods, with each assay having distinct
advantages and disadvantages of sensitivity, specificity,
throughput, cost and required expertise.
 For general diagnostic laboratories, most routinely tests
include indirect immunofluorescence using HEp2 cells and enzyme-
linked immunosorbent assays (ELISAs)/microplate ELISA –
Immunoblott (ANA profile)
Autoimmune Inflammatory Myopathies (AIMs) :
Autoantibodies detection
Z. Betteridge N. McHugh “Myositis-specific autoantibodies: an important tool to support diagnosis of

28. • Anti-nuclear antibodies (ANA) are immunoglobulin directed
against autologous cell nuclear and cytoplasmic components.
• Because of its high sensibility (90%), but relatively low
Specificity, detection of the ANA must be done by indirect
immunofluorescence (IIF) as screening test and all of those
positive samples are convenient to confirm its specificity by
ELISA, western blot or other techniques.
• Positive ANA detected by IIF must be evaluated taking in to
account the pattern and titer.
31
The role of ANA-IIF in the diagnostic work-up of
idiopathic inflammatory myopathies
Autoimmune Inflammatory Myopathies (AIMs) :
Autoantibodies detection

29. The role of ANA in the diagnostic work-up of idiopathic
inflammatory myopathies
 Detection of anti-nuclear antibodies (ANA), as detected by an
indirect immunofluorescence assay (IIFA) on HEp-2 cells, is
considered the most optimal screening assay for
autoantibodies in the SARD
 Immunofluorescence is one of the most commonly used methods
for testing autoantibodies; however, the assay requires
specialist skills to review the patterns and, in the case of
myositis autoantibodies, the results are often negative or
nonspecific, in particular for the anti-ARS autoantibodies
Autoimmune Inflammatory Myopathies (AIMs) :
Autoantibodies detection
Z. Betteridge N. McHugh “Myositis-specific autoantibodies: an important tool to support diagnosis of

30. Autoimmune Inflammatory Myopathies (AIMs) :
Autoantibodies detection

31. Autoimmune Inflammatory Myopathies (AIMs) :
Autoantibody Status
Myositis-specific autoantibodies (MSAs)
for further
differentiation
using other method
ELISA- Immunoblott
ANA can be an initial sc
Cytoplasmic Pattern
could be interpreted
as negative for ANA
IIFT because of
reporting differences
between laboratories.

32. Autoimmune Inflammatory
Myopathies (AIMs)
Immunoassays for the
detection of myositis-
specific autoantibodies
Line immunoassay / Immuno Blott:
Differentiation of antibodies
against cell nuclei (ANA)
often used to confirm the
presence of anti-Jo-1, after the
IIF method is commonly used.

33. Immunoassays for the detection of myositis-
specific autoantibodies
The most frequently evidenced in myositis
Autoantibodies and Useful for Clinical of
ASS AutoAntibodies Testing
 In cases of ASS, mostly anti-Jo1, anti-
PL7, and PL12 are detected
 Development of myositis first in anti-
Jo1 ASS,
 Development of ILD first in anti-PL7 and
PL12 ASS
 Useless for follow-up, not correlated
with disease activity

34. SUMMARY
• Autoantibodies are useful in diagnosis, prognosis and
disease progression prediction
• Choice in the type of AutoAntibodies tested should be
carefully evaluated according to clinical context for each
patient
• Importantly, to properly handle the clinical usefulness of
AutoAntibodies detection, clinician should also be aware
of both the advantages and the limits of the methods used
to test AutoAntibodies , to support the clinical
evaluation

35. Thank you