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Cell Biochemistry Martinsried |
G.Valet, Th.Dörner1)
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1. Background:a
Systemic lupus erythematosus (SLE) is an
autoimmune disease
with various inflammatory organ manifestations.
The presence of anti-DNA antibodies accompanied by abnomalities in
complement system, B-cell activity, T-B-cell interaction and
phagocytosis are typical features of deviated immune functions in SLE.
Disease activity is commonly described by the systemic lupus
erythematosus disease indicator (
SLEDAI)
which is determined from a variety of clinical parameters.
2. Goal: Considering the commonly altered B-cell activity in SLE it was investigated to which extent blood levels of CD27highpos plasma cells, CD27neg naive B-cells and CD19pos B-cells were associated with SLEDAI0-8 and SLEDAI>8> patients.
3. Results:
The algorithmic (non parametric) classification of the available
immunophenotype parameters
(fig.1)
shows that the immunophenotype parameters indicate
SLE activity better
(fig.2A)
than the clinical and clinical chemistry parameters
or all parameters together
(fig.2B/C).
The selected immunophenotype parameters of the
disease classification masks indicate increased
frequency of CD19pos, CD27highpos/CD20neg
and absolute counts of CD27highpos/CD20neg peripheral blood B-cells
in conjunction with decreased frequency and absolute counts
of CD27neg/CD20pos B-cells
(fig.3A).
Increased (+) anti-DNA antibodies, circulating
immune complexes (CIC), mucocutaneous or acute renal
manifestations and ESR are the most discriminatory
of the clinical and clinical chemistry parameters
(fig.3B)
while the classification of all parameters results
in a mixture of both parameter types
(fig.3C)
The reclassification of the learning set shows
correct classification in most instances with mask
coincidence factors between 0.60-1.00. This indicates
that already a partial fit of the patient classification masks
with the two disease classification masks SLEDAI0-8
and SLEDAI>8 is frequently sufficient for correct classifications
(fig.4).
4. Conclusion and Outlook:
Immunophenotype parameters indicate SLE disease activity to
a higher degree than clinical and clinical chemistry parameters.
Work in progress shows in addition that B-cell parameters in conjunction
with clinical parameters permit to predict therapy
responder and nonresponder patients with predictive values between
85-90%.
The observed discriminatory parameter patterns altogether
underline the importance for the further collection of
cellular parameters as equivalents
of actual disease processes and future disease development.
Literature References:
L1.
Jacobi A.M., M.Odendahl, K.Reiter, A.Bruns, G.M.Burmester,
A.Radbruch, G.Valet, P.E.Lipsky, Th.Dörner:
Correlation between circulating CD27high plasma cells and disease
activity in patients with systemic lupus erythematosus.
Arthritis & Rheumatism (2003) in press
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