The Lupus Book: A Guide for Patients and Their Families, Third Edition (4 page)

marizes some of the studies relating to sex and incidence.

Who Gets Lupus?

[13]

Table 4.1.
Sex Ratios at Age of Onset

or at First Diagnosis of SLE

Age

Female-to-Male Ratio

0–4

1.4:1

5–9

2.3:1

10–14

5.8:1

15–19

5.4:1

20–29

7.5:1

30–39

8.1:1

40–49

5.2:1

50–59

3.9:1

60–69

2.2:1

RACE AND GEOGRAPHY

The
incidence
of a disease is defined as the number of new cases per time period (e.g., year), whereas
prevalence
denotes the number of sufferers in the population. In the United States, African Americans, Latinos, and Asians have a

greater incidence of SLE than Caucasians. The prevalence among African Amer-

ican women was estimated by Kaiser-Permanente to be 286 per 100,000 in San

Francisco. A Hawaiian study showed that Asian women had three times the

prevalence rate of SLE as compared with Caucasian women. American Indians

seem to have the highest prevalence of lupus ever reported, but the numbers

surveyed were too small to confirm this trend.

Within these broad groupings, geography and racial characteristics may influ-

ence the prevalence of lupus. For example, lupus is very rare on the African

continent in comparison with the prevalence figures we see in the United States.

It is much more common in the Philippines and in China than it is in Japan,

and Sioux Indians have ten times the incidence of lupus as compared to other

American Indian tribes. Asians more often tend to have severe organ-threatening disease compared with other demographic groupings, closely followed by African American males.

WHY DO PEOPLE GET LUPUS?

Lupus results when a specific predisposing set of genes is exposed to the right combination of environmental elements, infectious agents, lupus-inducing drugs, excessive ultraviolet light, physical trauma, emotional stress, or other factors.

The next few chapters detail the circumstances that make certain populations

more susceptible to the disorder than others.

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Part II

INFLAMMATION AND

IMMUNITY

Part I defined and classified lupus, explored the historical context of this disease, and reviewed the populations lupus afflicts. The next two parts look at how it

damages body tissue and why it occurs. Scientifically speaking, this is the most difficult part of the book, because we tackle complex immunologic concepts and

discuss how inflammation takes place. Tables and summaries are provided

throughout to assist the reader. Feel free to skip this section or skim it. First, we turn to the workings of the normal immune and inflammatory response so

that the abnormal responses observed in lupus will be better understood.

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5

The Body’s Protection Plan

Inflammatory and immune responses account for many of the symptoms ob-

served in systemic lupus. This chapter reviews concepts of immunity and

inflammation; the following chapters discuss how these concepts apply to rheu-

matic diseases.

WHAT ARE THE COMPONENTS OF THE NORMAL

INFLAMMATORY AND IMMUNE SYSTEM?

The body is always on the lookout for foreign substances that may pose a threat to its intricate workings. Its monitoring system consists of blood and tissue

components, including certain proteins and blood cells that travel back and forth between blood and tissues.

Blood Components

A 150-pound (70-kilogram) person has about 6 liters of blood, which contains

several components. These include
red blood cells
, called
erythrocytes
, which are responsible for carrying and exchanging oxygen. If a person has a low count of red blood cells, she is suffering from anemia.
White blood cells
, call
leukocytes
, constitute the body’s main defense system. Other blood components are
platelets
, which clot blood, and
plasma
, which includes serum. Plasma makes up most of our blood volume. It contains many proteins and other substances

being carried to different parts of the body, including clotting factors that are not present in serum.

White blood cells
play a central role in inflammation. Five types of white blood cells have been identified by scientists; all are relevant to lupus. These include the following:

Polymorphonuclear cells
. These cells are also called
neutrophils
or
granulocytes
and, like all other blood components, they are made in our bone marrow (blood-making parts of our bone in the pelvis and sternum). After

[18]

Inflammation and Immunity

being produced, they circulate in the blood for a few days and then pass into

tissues. Some 50 to 70 percent of our circulating white cells are neutrophils.

Eosinophils
. These white blood cells make up 0 to 5 percent of all our white blood cells. Their life cycle is similar to that of granulocytes. Eosinophils are involved in allergic responses.

Basophils
. These cells do not have a clearly defined function and constitute less than 1 percent of our white blood cells. Tissue-based basophils are termed
mast cells
. These specialized cells combat parasitic or fungal invasion. They also play a role in allergy.

Lymphocytes
. These make up 20 to 45 percent of our white blood cells and are the gatekeepers of our immune responses. Produced in the bone marrow,

they migrate constantly between blood and tissue and can survive as long as

20 years. Lymphocytes can be T (thymus-derived) or B (derived from the

mythical ‘‘Bursa of Fabricius’’) cells.

Monocytes
. These cells represent about 5 percent of our circulating blood cells. They are the circulating blood component of what is called the

‘‘monocyte-macrophage’’
network because these cells are responsible for processing foreign materials (antigens) and the destroying cells and tissue

debris that are by-products of inflammation. In circulating blood, these cells

are called monocytes; macrophages can also be present in blood, but they are

mostly in tissues (see Table 5.1, Figures 5.1 and 5.3).

Lymphoid Tissue and the Thymus

Lymphoid tissue is a key part of the immune system and represents up to 3

percent of a person’s body weight. It includes our
lymph nodes
(or lymph glands), the
circulating lymphocytes
, and fixed
lymphoid tissue
(i.e., spleen). A 150-pound person has 1012, or 100 billion lymphocytes. They are widely distributed throughout the body and consist of long- and short-lived populations.

Bone marrow is the source of primitive ancestors of the
T
and
B lymphocytes
.

These precursors migrate to the thymus, a gland just below the neck, which

processes them into immunologically competent and knowledgeable
T cells
.

These T cells provide cellular immunity and are the body’s memory cells. About

70 percent of the lymphocytes are T cells. They remember what is foreign, go

on to alert the body when a person reencounters a foreign substance, and for-

mulate a response that protects the body.

Blood is carried to tissues by the arteries, and returns to the heart through the veins. Blood components, cellular waste and debris, and other materials can also return by another system—a chain of
lymph nodes
that starts in our toes and fingers and ends up in the chest area.

Lymphoid tissue contains T cells,
B cells
, and
natural killer cells
. B cells, RED BLOOD CELLS

MONOCYTES

BONE

WHITE BLOOD CELLS

Th-1 CELLS

MARROW

CD4 (T-Helper)

Th-2 CELLS

T CELLS

CD8 (T-Suppressor)

B CELLS

PLASMA CELLS

LYMPHOCYTES

EOSINOPHILS

NATURAL

PLATELETS

KILLER CELLS

IMMUNOGLOBULIN

BASOPHILS

ANTIBODIES

POLYMORPHONUCLEAR CELLS

(Granulocytes)

Fig. 5.1.
Circulating Blood Cells

[20]

Inflammation and Immunity

which make up 10 to 15 percent of the lymphocytes, produce antibodies that

eliminate what is foreign. Natural killer cells destroy targeted cells without

having been sensitized to them in the past.

There are various types of T cells, which are identified by their surface mark-

ings and appearance. These types are labeled by the cumbersome term
cluster-determined
, or
CD
. Nearly all T cells have markers associated with
CD3. CD4

cells are those that ‘‘help’’ or promote immune responses, while
CD8
cells usually ‘‘suppress’’ or block the immune response. Approximately 50 percent

of T cells have the CD4 marker and 20 percent the CD8 marker. Other markers

are also present.

Our Antibody Response: The Gamma Globulins

When you were growing up, there may have been an occasion when your pe-

diatrician gave you gamma globulin shots to minimize certain infections that

were going around. A type of gamma globulin, called immunoglobulin, is re-

sponsible for our antibody response. In response to an antigen, or foreign sub-

stance, our bodies produce antibodies. With appropriate signaling by T cells, B

cells transform themselves into
plasma cells
. Plasma cells make immunoglobulins. These gamma globulins circulate in the plasma and protect the body from

infection and other foreign material. There are five types of immunoglobulins:

IgG (immunoglobulin G
) is the major antibody of plasma and the most im-

portant part of our antibody response. Most autoimmune diseases are char-

acterized by IgG autoantibodies.

IgM
is initially produced to fight antigens but soon decreases and allows IgG

to take over. It plays an important but secondary role in autoimmunity.

IgA
is the major antibody of external secretions (tears, gastrointestinal tract secretions, and respiratory tract secretions). It is important in Sjo¨gren’s syndrome (a combination of dry eyes, dry mouth, and arthritis seen in many

lupus patients) and autoimmune diseases of the bowel (ulcerative colitis and

Crohn’s).

IgD
is poorly understood but has a role in helping B cells recognize antigens.

IgE
binds to mast cells and mediates allergic reactions.

This categorization is summarized in Table 5.1 and Figure 5.1.

And Finally, Cytokines and Complement

Cytokines
are hormonelike substances that promote various activities in the body, but in lupus, their functions are altered. Cytokines play a role in the

growth and development of cells, and include various interleukins and interfer-

The Body’s Protection Plan

[21]

Table 5.1.
Circulating Components of Whole Blood Important

to the Immune System

Red blood cells

Platelets

White blood cells (leukocytes)

Basophils (called mast cells in tissues)

Eosinophils

Polymorphonuclear cells (granulocytes, neutrophils)

Monocytes (called macrophages in tissues)

Lymphocytes

T cells

CD4 cells (helper)

CD8 cells (suppressor)

Natural killer cells

B cells

Plasma (includes serum)

Albumin

Globulin

Alpha globulins

Beta globulins (includes complement)

Gamma globulins (includes immunoglobulins, listed below)

IgG

IgA

IgM

IgD

IgE

Cytokines

ons. For example, interleukin-1 has many actions. Secreted during the course of an immune response, it exerts effects by binding to receptors on the cell surface.

Interleukin-1 can stimulate T cells to make interleukin-2, trigger the liver to make chemicals that perpetuate inflammation, allow certain cells to proliferate, and promote the production of growth factors which, in turn, make more white

blood cells and other growth factors, thus amplifying or ‘‘gearing up’’ the im-

mune system. Interferons were originally described as proteins which interfered with the growth of viruses. Their levels are increased in the sera of lupus patients and are probably important in the inflammatory process.

Cytokines are made by a variety of cells, especially lymphocytes and mac-

rophages. CD4 helper cells elaborate cytokines which promote inflammation.

They are called
Th-1
, or T helper-one cells, and go by several names: interferon gamma, interleukin-2, and tumor necrosis factor beta. Other CD4 helper cells

can promote the formation of antibodies, such as interleukins-4,6,10, and 13;

these are known as
Th-2
, or T helper-two cells, and fight inflammation. Table 5.2 lists some of the more important cytokines.

Complement
refers to a group of 28 plasma proteins whose interactions clear away immune complexes (antigens mixed with antibodies) and kill bacteria.

[22]

Inflammation and Immunity

Table 5.2.
Important Cytokines in Rheumatic Diseases

TNF-alpha

promotes rheumatoid-like inflammation. Blocked by 3 available

drugs: Enbrel, Remicade, and Humira