Absolute and Relative Blood Lymphocyte Subset Counts before and during Treatment of Patients with Thrombotic Thrombocytopenic Purpura (TTP).
Authors: Axdorph Ulla A. , Elias Maha , Hansson Mona , Hovinga Johanna A. Kremer , Lammle Bernhard , Bjorkholm Magnus 
Published: April 2020

Background. Although the discovery of autoantibody-mediated ADAMTS-13 deficiency has contributed to the understanding of acquired TTP, the pathogenesis of TTP is not fully elucidated. We analyzed absolute and relative counts of T-, B- and natural killer (NK) cells during treatment and in relation to ADAMTS-13 activity.

Material and methods. Nine consecutive patients (pts; 3 male, 6 female; median age 53, range 22–76 years) with acquired TTP were included. All pts had daily therapeutic plasma exchange (TPE) with fresh frozen plasma (FFP). The median number of TPE was 14 (range 3–38). Observation time was 53 months (median; range 3–71). All pts achieved clinical remission, however 2 pts still have dialysis at follow-up (no 2 and 8). One pat relapsed (no 8), but responded to 22 TPE. ADAMTS-13 activity was analyzed before start of TPE and twice during the following month. Inhibitory antibodies to ADAMTS-13 was analyzed in pts with ADAMTS-13 activity &lt;15%. Lymphocyte subsets (CD3, CD4, CD8, CD19/20, CD56) were analyzed on whole blood by flow cytometry using repeated analyses during the first month of treatment (median 4 analyses; range 3–5).

Results. See tables 1 and 2.

Patient characteristics and ADAMTS-13 Pat no Underlying disease Auto-ab (others than ab against AD-13) Number of TPE Corticosteroids Additional treatment AD-13 activity before TPE (%) Inhibitory AD-13 ab (BU/ml) Ab = antibody, AD-13 = ADAMTS-13, ND = not done 1 RA, psoriasis RF IgA 3 No - &lt;3 &gt;&gt;2 2 Fanconi anemia, hypothyroidism Thyroid antigen, P-ANCA 14 No - &lt;3 &gt;&gt;2 3 SLE, psoriasis ANA 9 Yes - &lt;3 &gt;&gt;2 4 - P-ANCA 12 Yes - &lt;5 &gt;&gt;2 5 SLE ANA, SSA, SSB 16 Yes Cyclophosphamide, vincristine &lt;5 &gt;&gt;2 6 - Cardiolipin, β2-glycoprotein 9 Yes - 50 ND 7 - - 20 Yes - 60 ND 8 Ca mammae, MGUS, psoriasis - 38 Yes Cyclophosphamide, vincristine rituximab, splenectomy 75 ND 9 MGUS - 17 Yes - 30 ND Absolute and relative blood lymphocyte subset counts before and during treatment Pat no Absolute/relative CD19/20 counts above normal range pretreatment Absolute/relative CD3 counts below normal range pretreatment Changes in absolute/relative blood lymphocyte counts during treatment CD3 CD19/20 CD56 ↑↔↓ = indicates increasing, decreasing or unchanged values during the observed treatment period, *borderline to decreased value 1 No/Yes Yes/Yes ↑/↔ ↔/↓ ↑/↑ 2 No/No No/No ↔/↔ ↔/↔ ↔/↔ 3 Yes/Yes No/Yes ↑/↑ ↓/↓ ↔/↔ 4 Yes/Yes Yes/Yes ↔/↑ ↓/↓ ↔/↔ 5 No/Yes Yes/Yes ↑/↑ ↓/↓ ↔/↔ 6 No/Yes Yes/Yes ↑/↑ ↓/↓ ↓/↓ 7 No/No Yes/No ↑/↔ ↔/↓ ↔/↔ 8 No/Yes Yes/Yes* ↔/↑ ↓/↓ ↔/↔ 9 No/No Yes/No ↔/↔ ↔/↔ ↔/↔

Conclusions. Five of nine (56%) pts had severe autoantibody-mediated ADAMTS-13 deficiency. These five pts had other autoantibodies in addition. Increased CD19/20 and decreased CD3 relative lymphocyte counts pretreatment were found in six pts, among them four with severe ADAMTS-13 deficiency. All but one normalized these counts during treatment. Further studies are needed in order to evaluate disturbancies in the relation of lymphocyte subsets in acquired TTP.