INT153260

Context Info Confidence 0.70 First Reported 2005 Last Reported 2008 Negated 2 Speculated 0 Reported most in Body Documents 19 Total Number 20 Disease Relevance 8.35 Pain Relevance 0.39

cell adhesion (CD22) plasma membrane (CD22)

Anatomy Link Frequency B cells 11 plasma cells 3 stem 1 CD22 (Homo sapiens)

Pain Link Frequency Relevance Heat antagonist 6 99.72 abatacept 1 90.40 cytokine 10 89.72 Inflammation 2 60.76 corticosteroid 39 55.60 Pain 37 45.00 visual analogue scale 22 32.44 Central nervous system 4 23.68 Arthritis 2 7.12 rheumatoid arthritis 39 5.00

Disease Link Frequency Relevance Heat Lymphatic System Cancer 147 99.76 Syndrome 97 99.72 Apoptosis 11 99.28 Histiocytic Sarcoma 33 99.14 Diffuse Large B-cell Lymphoma 1 98.80 Malignant Neoplastic Disease 20 98.52 Chronic Lymphoid Leukemia 11 97.76 Cancer 156 97.52 Fatigue 224 96.16 Autoimmune Disease 159 95.24

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Anatomy

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Speculation

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Disease term

Because dysregulated expression of CD22 could lead to excessive activation of B cells and autoantibody production [17], targeting this coreceptor in systemic autoimmunity appears to be a potentially new therapeutic pathway.

Gene_expression (expression) of CD22 in B cells associated with autoimmune disease

1) Confidence 0.70 Published 2006 Journal Arthritis Res Ther Section Body Doc Link PMC1779377 Disease Relevance 0.26 Pain Relevance 0

CD22 is expressed at low levels on immature B cells, expressed at higher levels on mature IgM+, IgD+ B cells, and absent on differentiated plasma cells.

Neg (absent) Gene_expression (expressed) of CD22 in plasma cells

2) Confidence 0.70 Published 2006 Journal Arthritis Res Ther Section Body Doc Link PMC1779377 Disease Relevance 0.49 Pain Relevance 0

Considering the low scattering of CD22 expression on normal B-lymphocytes, we determined a range of normal values and the median CD22 fluorescence on 33 blood samples from normal healthy volunteers.

Gene_expression (expression) of CD22 in B-lymphocytes

3) Confidence 0.70 Published 2006 Journal Arthritis Res Ther Section Body Doc Link PMC1779377 Disease Relevance 0.10 Pain Relevance 0

These new therapies are: (1) "B lymphocyte (BL)" inhibitors such as anti-CD20 monoclonal antibody, anti-CD22 monoclonal antibody, BlyS antagonists, tolerogens of pathogenic-antibody secreting LB (LJP 394) and edratide; (2) "Inhibitors of the costimulation" between antigen-presenting cells and T lymphocyte (TL) like monoclonal anti-CD40 ligand antibody or CTLA-4-Ig (abatacept); (3) "Cytokine antagonists" inhibiting key cytokines of SLE: interleukin-10, interferon-alpha, interleukin-6 and TNF.

Gene_expression (antibody) of CD22 in B lymphocyte associated with antagonist, abatacept, systemic lupus erythematosus and cytokine

4) Confidence 0.65 Published 2008 Journal Rev Med Interne Section Abstract Doc Link 18619716 Disease Relevance 0.43 Pain Relevance 0.27

CD22 is first expressed in the cytoplasm of pro-B and pre-B cells, and then on the surface of B cells as they mature, with expression ceasing with B cell differentiation into plasma cells [23].

Gene_expression (expressed) of CD22 in plasma cells

5) Confidence 0.64 Published 2006 Journal Arthritis Res Ther Section Body Doc Link PMC1526638 Disease Relevance 0.18 Pain Relevance 0

CD22 is expressed at low levels on immature B cells, expressed at higher levels on mature IgM+, IgD+ B cells, and absent on differentiated plasma cells.

Neg (absent) Gene_expression (expressed) of CD22 in plasma cells

6) Confidence 0.61 Published 2006 Journal Arthritis Res Ther Section Body Doc Link PMC1779377 Disease Relevance 0.49 Pain Relevance 0

Monoclonal antibodies used in this study were CD19 allophycocyanin (APC) (clone SJ25C1) and CD22 phycoerythrin (PE) (clone S-HCL-1).

Gene_expression (phycoerythrin) of CD22

7) Confidence 0.61 Published 2006 Journal Arthritis Res Ther Section Body Doc Link PMC1779377 Disease Relevance 0.12 Pain Relevance 0

Therefore, CD22 is an attractive molecular target for therapy because of its restricted expression; it is not exposed on embryonic stem or pre-B cells, nor is it normally shed from the surface of antigen-bearing cells.

Gene_expression (expression) of CD22 in stem

8) Confidence 0.55 Published 2006 Journal Arthritis Res Ther Section Body Doc Link PMC1526638 Disease Relevance 0.16 Pain Relevance 0

The expression of CD22 is specific to B-cells and is developmentally regulated so that it is expressed at low levels in the cytoplasm of pro-B and pre-B-cells, and its localization shifts to the cell surface and higher expression on mature IgM+, IgD+ B-cells (Dörken et al 1986).

Gene_expression (expression) of CD22 in B-cells

9) Confidence 0.54 Published 2007 Journal Therapeutics and Clinical Risk Management Section Body Doc Link PMC2376077 Disease Relevance 0.26 Pain Relevance 0.06

CD22 is strongly expressed on follicular, mantle, and marginal-zone B-cells, but is weakly present in germinal B-cells (reviewed in (Nitschke 2005; Tedder et al 2005b)).

Gene_expression (expressed) of CD22 in B-cells

10) Confidence 0.54 Published 2007 Journal Therapeutics and Clinical Risk Management Section Body Doc Link PMC2376077 Disease Relevance 0 Pain Relevance 0.03

In addition, we report here, for the first time, that patients with pSS have a CD22 over-expression in their peripheral B cells, which was downregulated by epratuzumab for at least 12 weeks after the therapy.

Gene_expression (expression) of CD22 in B cells

11) Confidence 0.54 Published 2006 Journal Arthritis Res Ther Section Body Doc Link PMC1779377 Disease Relevance 0.58 Pain Relevance 0

This is consistent with the finding that patients with Sjögren's syndrome have an over-expression of CD22.

Gene_expression (expression) of CD22 associated with syndrome

12) Confidence 0.54 Published 2006 Journal Arthritis Res Ther Section Body Doc Link PMC1779377 Disease Relevance 0.10 Pain Relevance 0

At the final evaluation, all the patients recovered to the same increased CD22 expression compared with normal, as observed in patients with untreated pSS.

Gene_expression (expression) of CD22

13) Confidence 0.54 Published 2006 Journal Arthritis Res Ther Section Body Doc Link PMC1779377 Disease Relevance 0.08 Pain Relevance 0

Further, we determined that pSS patients have a CD22 over-expression in their peripheral B cells, which was downregulated by epratuzumab for at least 12 weeks after the therapy.

Gene_expression (over-expression) of CD22 in B cells

14) Confidence 0.54 Published 2006 Journal Arthritis Res Ther Section Abstract Doc Link PMC1779377 Disease Relevance 0.17 Pain Relevance 0

In addition, we report here, for the first time, that patients with pSS have a CD22 over-expression in their peripheral B cells, which was downregulated by epratuzumab for at least 12 weeks after the therapy.

Gene_expression (over) of CD22 in B cells

15) Confidence 0.54 Published 2006 Journal Arthritis Res Ther Section Body Doc Link PMC1779377 Disease Relevance 0.58 Pain Relevance 0

In addition, we report here, for the first time, that patients with pSS have a CD22 over-expression in their peripheral B cells, which was downregulated by epratuzumab for at least 12 weeks after the therapy.

Gene_expression (-) of CD22 in B cells

16) Confidence 0.54 Published 2006 Journal Arthritis Res Ther Section Body Doc Link PMC1779377 Disease Relevance 0.58 Pain Relevance 0

CD22 is expressed on the surface of normal mature and malignant B lymphocytes.

Gene_expression (expressed) of CD22 in B lymphocytes associated with malignant neoplastic disease

17) Confidence 0.52 Published 2007 Journal Clin Rev Allergy Immunol Section Body Doc Link PMC2071970 Disease Relevance 0.70 Pain Relevance 0

In contrast to HS, diffuse large B-cell lymphoma constantly express various pan-B markers such as CD19, CD20, CD22, and CD79a, while anaplastic large cell lymphomas are positive for CD30, and ALK [1].

Gene_expression (express) of CD22 in B-cell associated with lymphatic system cancer, histiocytic sarcoma and diffuse large b-cell lymphoma

18) Confidence 0.26 Published 2007 Journal Diagn Pathol Section Body Doc Link PMC1808440 Disease Relevance 1.62 Pain Relevance 0.03

This might explain why most progress has been made so far in the clinical development of antibody toxins that target cell surface molecules such as CD22 and CD25 expressed on certain malignancies of hematologic origin [34,35], where tumor cells are usually more accessible.

Gene_expression (expressed) of CD22 associated with cancer

19) Confidence 0.26 Published 2005 Journal Breast Cancer Res Section Body Doc Link PMC1242130 Disease Relevance 0.73 Pain Relevance 0

This might explain why most progress has been made so far in the clinical development of antibody toxins that target cell surface molecules such as CD22 and CD25 expressed on certain malignancies of hematologic origin [34,35], where tumor cells are usually more accessible.

Gene_expression (expressed) of CD22 associated with cancer

20) Confidence 0.22 Published 2005 Journal Breast Cancer Res Section Body Doc Link PMC1242130 Disease Relevance 0.73 Pain Relevance 0

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