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Thursday, 28 April 2016

ANTI SS/RO AND ANTI SSB/LA IN A PATIENT WITH SJÖGREN SYNDROME

Written by Vanessa García Moreira | Angélica Cienfuegos González | Carlos Blanco Cristóbal, Posted in Volumen 2

Pictures 1 and 2 show a well of a plate indirect immunofluorescence (IIF) of Hep-2000® cells with a 1/2560 speckled pattern corresponding to anti-SSA/Ro (Ro60+Ro52) and anti-SSB/La antibody (lat-er demonstrated by immunoblotting in the picture 3).

Hep-2000® cells are squamous cell carcinoma of human esophagus which have been transfected with cDNA encoding the antigen SSA/Ro 60 KDa, thus conferring greater antigenic expression that increases specificity and sensitivity for the determination of these autoantibodies.
Articulo1 imagen1 500x374Figure 1. Fine speckled pattern in most of the cells in negative metaphase, while 10-20% of the cells show a fine speckled with positive staining of the nucleoli.
 
In the images 1 and 2 there is a speckled pattern with prominent nucleoli staining in the 10-20% of the interphase nuclei. Rest of the interphase nuclei show a fine speckled pattern. The chromosome region of nuclei in mitotic metaphase is negative.

Articulo1 imagen2 500x374Figure 2. Same pattern as in the previous picture, where better appreciate the negative metaphases.

Sample corresponds to a 51-year-old cleaner profession, smoking one pack/day, no drug allergies or known metabolic disorders, who comes to consulting your primary care physician referring populous lesions, winy red, in both lower extremities, from about a year ago. They are self-limited injuries, about 3-4 days duration and recurring. Further relates edemas in the lower limbs that are not objectified in exploration. She reported loss of weight and hair. There is no photographic reference of injuries patient.

Articulo1 imagen3 500x214Figure 3. Immunoblot where positivity is evidence for the autoantibodies anti-SSA/Ro52, anti SSA/Ro60 y anti SSB/La.
 
In the analytical requested by your primary care physician only highlights a rheumatoid factor >500 IU/mL (0-15), and therefore requests the rheumatology service assessment, which completes  studies. No signs of joint inflammation or other systemic symptoms in outbreaks. After the anamnesis, physical examination and results of antinuclear antibodies (ANA), was diagnosed with Sjögren's syndrome.

Sjogren's Syndrome, a disease described in 1930 by the Swedish ophthalmologist Henrik Sjögren1, is a chronic autoimmune exocrinopathy, characterized by an infiltration of T lymphocytes in the affect glands and systemic activation of B lymphocytes have a slow progression and an unknown etiology.

It affects 0.5-3% of the population, mostly middle-aged women, although it can occur at any age2. Evolves very slowly lapsing more than 10 years between the onset of symptoms and full development.

It is considered as primary SS (pSS) if it appears in isolation and secondary if it occurs associated with other autoimmune diseases such as systemic lupus erythematosus or rheumatoid arthritis.

The cause is unknown. They have been described several possible triggers as environmental (viral infections) and hormone (estrogen, androgen deficiency), which would result in genetically susceptible subjects, in an inadequate response to certain exocrine glandular epithelium members as the Ro and La ribonucleoproteins. pSS patients often have antibodies to SSA/Ro or SSB/La, and many patients have both at once. The frequency of anti-SSA/Ro and/or anti-SSB/La varies between studies, but usually 60 to 80 percent of patients with pSS have one or both of these autoantibodies. The study of SSA/Ro revealed that consists of two different antigens, one of 60 kDa and other of 52 kDa3. pSS patients may develop autoantibodies to either or both antigens4.

It is mainly characterized by dryness of the oral mucosa (xerostomia) and eye (xerophthalmia), although it can often produce symptoms nasal dryness, skin or vaginal. However, the inflammatory reaction can affect systemically to various organs and cause extraglandular manifestations. The extraglandular manifestations are diverse and sometimes can be the presentation of the disease as in this case. The most common are arthralgia (65 %), Raynaud's phenomenon (40 %), lymphadenopathy (20 %) and pleuropulmonary, kidney or liver disorders with about 10 % each one. There are less frequent manifestations such as vasculitis, peripheral neuropathies, lymphomas, splenomegaly or myositis.

Regarding laboratory data, it may appear an elevated erythrocyte sedimentation rate in 60-90% of cases and gamma-glutamyltranferase, C-reactive protein (5%), leukopenia, thrombocytopenia, anemia, increased transaminases or alkaline phosphatase. More specific data are positive ANA that appear in 90 % of cases, anti-SSA/Ro (55%) or anti-SSB/La (40%) and elevation FR (60-90 %).

The anti-SSA/Ro and anti-SSB/La antibodies are particularly important in the SS. Usually they associated with disease duration. They are particularly associated with extraglandular manifestations, in particular with vasculitis. About 10-15% of patients with pSS present purpura (as our patient), mainly in the form of vasculitis. The small vessel leukocytoclastic vasculitis is the most common histological pattern (95 %). Usually it occurs in most palpable purpura not associated with cryoglobulins and less frequently associated with cryoglobulinemic urticarial.

References

  • Sjögren H. ZurKenntnis der Keratoconjunctivitis sicca. ActaOphthalomol 1933; 11(suppl II):1.
  • Thomas E, Hay EM, Hajeer A, Silman AJ. Sjögren's syndrome: a community-based study of prevalence and impact. Br J Rheumatol 1998; 37:1069.
  • Chan EK, Tan EM, Ward DC, Matera AG. Human 60-kDa SS-A/Ro ribonucleoprotein autoantigen gene (SSA2) localized to 1q31 by fluorescence in situ hybridization. Genomics 1994; 23:298.
  • Ben-Chetrit E, Chan EK, Sullivan KF, Tan EM. A 52-kD protein is a novel component of the SS-A/Ro antigenic particle. J Exp Med 1988; 167:1560.
  • http://www.anapatterns.org/
  • Tzioufas AG, Voulgarelis M. Update on Sjögren's syndrome autoimmune epithelitis: from classification to increased neoplasias. Best Pract Res Clin Rheumatol. 2007;21(6):989-1010.

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