[CIS PIDD] [cis-pidd] Consult. Patient with an inflammatory-autoimmune syndrome, very and persistent low C4, lymphopenia, no response to immunosupressive drugs

[CIS-PIDD]

MEis an 8 years-old girl, with an inflammatory-autoimmune syndrome. Disease onsetwas at 4 years old. She has  normal exomesequencing (commercial laboratory).

Wewould be grateful if you could help us regarding molecular diagnostic andclinical manage

Medical record 

Familial antecedents

2maternal aunts, one with hypotiroidism and the other with JIA

Personal antecedents

Shebegan at 4 years old with an inflammatory picture: prolonged fever, elevatedinflammatory parameters, photosensibility, polyarthritis, leukocytoclasticvasculitis, moderate hepatitis (by liver biopsy it was characterized assteatosis).  Generalized weakness. No CNSor renal involvement. 

Duringher clinical course recurrent muguet was observed. Anaphylactoid reaction totrimetroprime sulphametoxazole (distress, angioedema). Specific bowelinflammation or lung disease was ruled out.

Remarkablelaboratory profile: anemia, progressive and severe lymphopenia, and elevatedtransaminases. 

Positiveautoantibodies: High titers of ANA, dsDNA, Sm,  RNP, Ro,  a/nuclesosome a/histone ASCA.

Noresponse to immunosuppressive drugs (azathioprine, mycophenolate) was observed,and progressively, she needs increased doseof corticosteroids for the management of her chronic and continuous clinicalpicture (intermittent fever, arthritis, general involvement). Hospitalizations due tosteroids morbidity (spinal crush and elevated eye pressure). We prescribedsirolimus treatment and it allowed decreased steroids doses to 6mg/d withgreater clinical stability during 2017.

 Nowadays she is hospitalized because abilateral thigh and arm edema and calcinosis progression plus respiratorycompromise in study.

 

Immunological laboratory

Slightly  decreased C1q levels. Very and persistentlow  C4. C3 and CH50 within normal range

Polyclonalhypergammaglobulinaemia

Intermediateproteic antibody response

Mildglobal polysaccharide response with drop of response within two years fromvaccine

ProgressiveLymphopenia

Adequaterelative number of naïve and memory T cells

Elevateddouble negative TCR alpha/beta T cells

Normalnumber of CD4 Th17 cells

ElevatedCD4+ CD127low T cells

Functionaltest were not performed due to lymphopenia 

 

Dueto her early autoimmflamatory-autoimmune disease onset being refractory toimmunosuppressive treatment  a probablemonogenic disease diagnosis is suspected. 

Inspite of she has a normal exome sequencing (commercial laboratory) this studycannot inform the patient copy number variation of complement component C4.

Doyou think that C4 low gene copy number variation could have relation with thepatient disease? If you consider this diagnose, is it available in yourlaboratory?

Whatdo you think regarding the treatment? Could the BMT be the best option? 

Couldthe BMT be the best option in spite of the C4 complement origin? 

 
I hope your help. Thank you very much
Andrea C Gómez Raccio
Inmunóloga-Pediatra
Inmunología
Hospital de Niños "Dr Ricardo Gutiérrez"
Ciudad Autónoma de Buenos Aires
Argentina
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