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Inhibition of natural killer cell activity by fibronectin.

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clinically and histologically consistent with SCL. Despite 6
months of therapy with oral hydroxychloroquine, 60 mg per
day of oral prednisone. and intralesional and heavy topical
steroid administration, the lesions persisted. A pulse of I gm
of methylprednisolone was administered intravenously on 3
successive mornings. He experienced clearing of pruritis and
inflammatory skin lesions within I week. Oral prednisone
was stopped and improvement persisted for over 3 months.
Management of lupus renal involvement with pulse
methylprednisolone therapy has been amply reported (2,3).
Less frequently, extra-renal manifestations of SLE, such as
central nervous system dysfunction, thrornbocytopenia, hemolytic anemia (4), serositis, lymphadenopathy, and vasculitic skin rash (3,have been managed with pulse methylprednisolone therapy. In this communication, we present
evidence of benefit of intravenous pulse methylprednisolone
in 2 patients with persistent lupus dermatitis not sufficiently
responsive to conventional therapy. The improvement lasted
over 2 months and allowed the discontinuation of oral
prednisone. The advantages in clinical improvement must be
weighed against the cost, intravenous administration, and
the rare, but reported, adverse effects.
Jerry W.Goldberg, MD
Martin D. Lidsky, MD
Veterans Administration Medical Center
and Baylor College of Medicine
Houston, TX
that approximately 10% of B27 positive relatives of an AS
patient will have AS, compared with approximately 2% of
relatives of B27 positive healthy subjects. Our own data are
in almost perfect accord with this.
Calin et al also suggested that "one would expect the
frequency of AS among relatives of B27 positive AS patients
to range from that found in a random B27 positive population
to a higher prevalence" (italics added), a comment with
which I think most would agree. Nevertheless, there seems
to be a paradox. The AS prevalence they quote for a random
B27 positive population (blood donors) is approximately
19Yehigher than the 10% prevalence found for B27 positive
AS relatives. This is the very opposite of what was anticipated.
As I have suggested elsewhere (31, perhaps the
explanation is that the population prevalence of ankylosing
spondylitis lies between the above 2% and 10% figures for
B27 positive subjects, and is probably nearer the 2% figure.
This would drop the accepted prevalence of AS in a white
population back to the earlier epidemiologic figures of 0. I0.5%. Certainly some 20% of B27 positive subjects with
nonspecific urethritis may develop a reactive arthritis but, as
has been amply demonstrated, this has little familial relationship with AS (4). There would therefore seem to be no a
priori reason why the 20% figure should apply to AS.
A. S. Russell, MD
The University of Alberta
Edmonton, Alberta
1. Sontheimer RD. Thomas JR, Gilliam JN: The clinical and immu-
1. Calin A, Marder A, Becks E, Burns T: Genetic differences
nological features of patients with subacute cutaneous lupus
erythematosus: a distinct LE subset (abstract). J Invest Dermatol
71:278, 1978
Cathcar! ES, Idelson BA, Scheinberg MA, Couser WG: Beneficial effects of methylprednisolone "pulsc" therapy in diffuse
proliferative lupus nephritis. Lancet i: 163-166, 1976
Nebout T, Sobel A, Lagrue G: Intravenous methylprednisolone
pulses in diffuse proliferative lupus nephritis. Lancet i:909, 1977
Eyanson S , Passo MH, Aldo-Benson MA, Benson MD: Methylprednisolone pulse therapy for nonrenal lupus erythematosus.
Ann Rheum Dis 39:377-380, 1980
Isenberg DA, Morrow WJW, Snaith ML: Methylprednisolone
pulse therapy in the treatment of systemic lupus erythematosus.
Ann Rheum Dis 41:347-351, 1982
Comment on Calin article
To the Editor:
Calin et al in their recent article ( I ) demonstrate, as
we have (2), that the prevalence of ankylosing spondylitis
(AS) varies in different groups of B27 positive subjects. It
was found to be much higher in B27 positive relatives of
probands with AS than in B27 positive relatives of healthy
control, B27 positive probands. Those authors calculated
between B27 positive patients with ankylosing spondylitis and
B27 positive healthy controls. Arthritis Rheum 26: 1460-1464,
2. Russell AS, LeClercq S: Spondyloarthropathy and HLA B27,
familial associations (abstract). Arthritis Rheum (suppl) 26:s 18,
3. LeClerq SA, Chaput LC, Russell AS: Ankylosing spondylitis: a
family study. J Rheumatol 10:629-632, 1983
4. Hochberg MC, Bias WA, Arnett FC: Family studies in HLA
associated arthritis. Medicine 5 7 4 3 - 4 7 4 . 1978
Inhibition of natural killer cell activity by fibronectin
To the Editor:
Natural killer (NK) cells play an important part in the
immunosurveillance of tumor development (1). 'Their function has been demonstrated to be modified by various
substances, including interferon (2) and prostaglandins (3).
Here we report that the major connective tissue constituent
fibronectin (FN) may function as another modulator of NK
activity. Fibronectin has been characterized extensively
(4.5) and has been shown to be synthesized by fibroblasts (6)
which secrete the glycoprotein into their environment.
Peripheral blood mononuclear cells derived from
Tablk 1. The influence of fibronectin upon natural killer cell
activitv in vitro
Effector:target cell ratios
per well ( p g )
50.6 2
21.6 2
32.3 2
43.6 2
50: 1
44.0 2
22.0 ?
28.4 2
38.4 2
25: I
33.9 2
25.9 2
33.6 2
33.5 2
* Data are given as mean percentage of lysis 2 standard crror of the
mean of 4 experiments.
healthy volunteers were used as effectors in ”Cr release
assays in which the myeloid leukemia cell line K562 was
used as target cell population. All assays were carried out in
triplicate in round-bottom microtiter plates (Nunc, Denmark) in a total volume of 0.2 ml in effector: target cell ratios
(E:T) of 100: 1, 50: 1, and 25: 1. NK assays were performed
either with or without fibronectin (The New York Blood
Centet, Inc.) in various concentrations (200 pg, 100 pg, and
50 pg per well). After an overnight incubation, the specific
lysis was calculated according to the formula:
% lysis =
‘P”experiment - ‘Omspontaneous lysis
CPmmaximumlysis - Cpmspontaneous
where maximum lysis was achieved by treatment of labeled
target cells with sodium dodecyl sulfate (Sigma, St. Louis,
Md). The mean 5 standard error of 4 experiments was
Table 1 shows that in E:T of 100: 1 and 50: 1 the NK
activity h a s inhibited by FN in a dose-dependent manner.
Interestingly, inhibition of NK activity by FN was only
marginal or did not occur at all in E:T of 25: I . Among other
explanations, this could be attributed to the fact that F N may
inhibit NK activity via a “bystander” cell which was present
in too low a concentration. Experiments to clarify this point
are currently under way in our laboratory. Microscopic
examination of peripheral blood rnononuclear cells incubated with FN in concentrations of 200 pg, 100 pg, and 50 pg
per well overnight showed that the inhibition of NK activity
was not due to an agglutination and trapping of effector cells.
Our rcsults suggest that FN might play a part in the
regulation and control of NK activity, although it is premature to say whether this effect is achievcd through direct
action upon the effector cell or by the induction of another
regulative substance. The presence of FN in the connective
tissue could rcsult in the suppression of NK activity, thus
leading to an impairment of immunosurveillance.
Christoph C. Zielinski, MD
Hans Peter Schwarz, MD
Vienna University Hospital
Vienna, Austria
1. Herberman RB, Ortaldo J R : Natural killer cells: their role in
defenses against disease. Science 214:24-30. 1981
2. Herberman RB. Ortaldo JR, Bonnard GD: Augmentation by
interferon of human natural and antibody-dependent cell-mediated cytotoxicity Nature 277:221-223. 1979
3. Brunda MJ, Herberman RB, Holden HT: Inhibition of munne
natural killer cell activity by prostaglandins. J lmmunol
124:2682-2687, 1980
4. Vaheri A, Mosher. DF: High molecular weight, cell surfaceassociated glycoprotein (fibronectin) lost in malignant transformation. Biochim Biophys Acta 516:l-25, 1978
5. Yamada KM. Olden K: Fibronectins: adhesive glycoproteins of
cell surface and blood. Nature 275:179-184. 1978
6. Ruoslahti E, Vaheri A , Kuusela P, Linder E: Fibroblast surface
antigen: a new serum protein. Biochim Biophys Acta 358:322352, 1973
Gout begins in the second century of life
To the Editor:
American society’s preoccupation for records has
spilled over into the rheumatology literature. Witness the
response generated by Dr. Yunus (1,2) regarding the largest
knee effusion aspirated. In that spirit, we wish to report what
we believe is the oldest patient to experience an initial attack
of gout.
A 101-year-old black female was admitted to Germantown Hospital and Medical Centet with progressive
difficulty with ambulation over a 2-week period because of
the acute onset of painful, swollen knees. Her joint disease
symptoms began 2 weeks earlier with transient left first
metatarsophalangeal (MTP) joint pain. There were no prior
episodes of any similar attacks of arthritis or gout according
to the patient, who was an excellent historian. Her medical
history was remarkably negative except for I hospitalization
30 years earlier for minor trauma. She had no history of
urolithiasis or hypertension. Prior to her illhess, she cared
for herself in her children’s home. Her medications included
only an occasional aspirin. She did not drink alcohol.
On physical examination her MTP joints were normal. Both knees were warm, swollen, and tender. There
were no tophi. Laboratory studies demonstrated an initial
uric acid concentration of 10.8 mg/dl, (repeat value 7.8),
blood urea nitrogen 16 mg/dl, creatinine 1 . 1 mg/dl. Radiographs of the knees revealed marked degenerative changes
without chondrocalcinosis. Forty cc of inflammatory fluid
was removed from the right knee, 60 cc from the left.
Synovial fluid analysis revealed a white blood cell count of
11 ,OOO (90% neutrophils) and many intra- and extracellular
monosodium urate crystals. N o calcium pyrophosphate
crystals were seen. Each knee was injected with a corticosteroid preparation and within 48 hours the patient could
once again walk. She was discharged with a regimen of
prophylactic colchicine therapy.
In the Framingham Study (3), the average age at the
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fibronectin, inhibition, natural, killer, activity, cells
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