Clinical case 1

A 75 year old patient who suffered from rheumatoid arthritis for 40 years visits the outpatient clinic. In the last years he
has always been surprised that he doesnt see more patients with extensive deformations of their hands in the
waiting room of the rheumatology department. He asks his rheumatologist how this is possible. The rheumatologist
replies that therapies (and therapy strategies) for rheumatoid arthritis have much improved in the last decades. The
deformations occur due to inflammation in the joints caused by aberrant actions of the immune system, which we are
able to target nowadays . During his lunch break the rheumatologist contemplates the working mechanisms of the
immune system and how we learnt to influence some of them in order to treat autoimmune disease, such as rheumatoid
arthritis.

1. What three (hypothetical) options can you think of to target active autoimmune disease and diminish
inflammation? (Choose all options)
a. Upregulation of Treg cells
True. hypothetically you would like to increase the role of Treg cells since they have a regulatory function and can
terminate an ongoing immune reaction.
b. Induction of apoptosis of autoreactive T cells/B cells
True. hypothetically you would like to specifically eliminate autoreactive T and/or B cells in a regulated way. In fact this
could be one of the instruments to prevent autoimmunity in the physiologic situation.
c. Upregulation of complement proteins
False. complement proteins have roles that augment and stimulate inflammation. On the contrary, the deficiency of
complement can lead to autoimmune disease most importantly because of impaired clearance of immune complexes.
d. Elimination of IL-17
True. IL-17 is a chemoattractant for neutrophils and may contribute to upregulation of inflammation. In fact, IL-17 is
studied as a therapeutic target in inflammatory arthritis.
e. Stimulation of dendritic cells to present cells of human synovial tissue to lymphocytes
False. presentation of autoantigens to lymphocytes (especially in an inflammatory context) could trigger an autoimmune
reaction.
f. Downregulation of endogenous corticoids
False. endogenous corticoids, like cortisol, suppress inflammation.
g. Promote T cell help to autoreactive B cells
False. T cell help will strengthen and increase B cell proliferation, therefore it should not be promoted in autoreactive B
cells. In fact, the lack of T cell help is one of the instruments to prevent autoimmune reactions of B cells in the
physiologic situation.

2. Which four pathologic pathways in rheumatoid arthritis can be influenced with commercially available
therapeutics at this moment? (Choose all options)
a. Inhibition of pro-inflammatory cytokines
True. in fact this is one of the most important pathways of biologicals. The pathways of several pro-inflammatory
cytokines can be blocked, such as TNF, IL-1 and IL-6.
b. Administration of exogenous corticoids
True. the administration of exogenous corticoids, like prednisolone, is one of the oldest therapies to suppress

inflammation.
c. Depletion of CD20+B cells
True. Rituximab is a monoclonal antibody that depletes CD20+ B cells and is known to decrease inflammation.
d. Depletion of CD4+ T cells
False. an agent to deplete CD4+ T cells is not available. A CD4+ T cell depleted state is seen in HIV patients, who are
severely immuno-incompetent and suffer from opportunistic infections. However they can also suffer from several
musculoskeletal problems including arthritis. Interestingly, depletion of CD4+ T cells was tried in rheumatoid arthritis in
the 1980s but had little effect.
e. The inhibition of co-stimulation molecules on the surface of T cells
True. abatacept it thought to interfere with the stimulation of T cells by binding CD80 and CD86 receptors that are
expressed by professional antigen-presenting cells such as B cells, macrophages and dendritic cells
f. The inhibition of specific pathogenic autoantibodies or specific autoantibody producing plasma cells
False. at this moment this not possible, however this is subject of current investigations.
Clinical case 2
A 23 year old law school student with SLE will be treated with rituximab. She has read a lot about the working
mechanism and asks her rheumatologist if it is not dangerous to have this therapy. Will she still be protected for the
diseases she was vaccinated for in her childhood (e.g. diphtheria, rubella)?

1. What is the correct reply?

a. No you are right, for 6 months you are not protected for these diseases, however after 6 months your B cells and the
protective antibodies will gradually come back. Until that time you have to be extra careful not to be exposed to diseased
persons.
False. rituximab only depletes CD20+ B cells, antibody production is not influenced much as plasma cells are
CD20-negative and are not depleted by a CD20-targeted therapy
b. Yes, you are still protected for these diseases, because T cells are pivotal for the immunologic memory and the
defence for this particular specific infectious disease, so it is not so important that your B cells are depleted.
False. although T cell also play a role in the immunologic memory. Protection for infectious diseases through
vaccinations mostly depends on protective antibodies.
c. Yes, you are still protected for the diseases you were vaccinated for, because long lived plasma cells that create the
immunologic memory are not depleted with rituximab.
True. this is right
d. No you are right, with rituximab the B cells are depleted. Therefor the immunologic memory for the diseases you are
vaccinated for, will be lost. You can be vaccinated again after 6 months, when your B cells come back.
False. the long lived plasma cells that create the immunologic memory are not depleted by rituximab